Causal Effect of Lp(a) [Lipoprotein(a)] Level on Ischemic Stroke and Alzheimer Disease: A Mendelian Randomization Study
Pan Y, Li H, Wang Y, Meng X, Wang Y.. Stroke, 2019-10-10
Topic: Amyloid, tau and blood-test diagnosis
Background and Purpose- Stroke and Alzheimer disease are 2 major causes of neurological disability in aged people and shared overlapping predictors. In recent prospective studies, high Lp(a) [lipoprotein(a)] level is associated with high risk of stroke but low risk of Alzheimer disease. Whether this reflects a causal association remains to be established. The aim of this study is to examine the causal associations of Lp(a) concentrations on ischemic stroke, ischemic stroke subtypes, and Alzheimer disease. Methods- We used 9 single-nucleotide polymorphisms associated with Lp(a) concentrations as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the Multiancestry Genome-Wide Association Study of Stroke consortium with European individuals ≤446 696 individuals. Summary-level data on Alzheimer disease were obtained from the International Genomics of Alzheimer Project With European individuals ≤54 162 individuals. Two-sample Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches, and MR-Egger regression was used to explore pleiotropy. Results- Genetically predicted 1-SD log-transformed increase in Lp(a) concentrations was associated with a substantial increase in risk of large artery stroke (odds ratio, 1.20; 95% CI, 1.11-1.30; P P =0.001) and Alzheimer disease (odds ratio, 0.94; 95% CI, 0.91-0.97; P <0.001) using inverse-variance weighted method. No significant association was observed for total ischemic stroke or cardioembolic stroke. MR-Egger indicated no evidence of pleiotropic bias. Results were broadly consistent in sensitivity analyses using penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches accounting for potential genetic pleiotropy or outliers. Conclusions- This study provides evidence to support that high Lp(a) concentrations was causally associated with an increased risk of large artery stroke but a decreased risk of small vessel stroke and Alzheimer disease. The mechanism underlying the double-edged sword effect of Lp(a) concentrations on neurological system requires further investigation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Pan, Y., Li, H., Wang, Y., & Meng, X. (2019). Causal Effect of Lp(a) [Lipoprotein(a)] Level on Ischemic Stroke and Alzheimer Disease: A Mendelian Randomization Study. Stroke. https://doi.org/10.1161/strokeaha.119.026872
Vancouver
Pan Y, Li H, Wang Y, Meng X. Causal Effect of Lp(a) [Lipoprotein(a)] Level on Ischemic Stroke and Alzheimer Disease: A Mendelian Randomization Study. Stroke. 2019. doi:10.1161/strokeaha.119.026872. PMID: 31597550.
BibTeX
@article{pan2019-31597550,
author = {Pan, Y. and Li, H. and Wang, Y. and Meng, X.},
title = {{Causal Effect of Lp(a) [Lipoprotein(a)] Level on Ischemic Stroke and Alzheimer Disease: A Mendelian Randomization Study}},
journal = {Stroke},
year = {2019},
doi = {10.1161/strokeaha.119.026872},
pmid = {31597550},
url = {https://doi.org/10.1161/strokeaha.119.026872}
}
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Key findings
- In recent prospective studies, high Lp(a) [lipoprotein(a)] level is associated with high risk of stroke but low risk of Alzheimer disease.
- Methods- We used 9 single-nucleotide polymorphisms associated with Lp(a) concentrations as instrumental variables.
- Results- Genetically predicted 1-SD log-transformed increase in Lp(a) concentrations was associated with a substantial increase in risk of large artery stroke (odds ratio, 1.20; 95% CI, 1.11-1.30; P <0.001) and a reduce in risk of small vessel stroke (odds ratio, 0.92; 95% CI, 0.88-0.97; P =0.001) and Alzheimer disease (odds ratio, 0.94; 95% CI, 0.91-0.97; P <0.001) using inverse-variance weighted method.
- No significant association was observed for total ischemic stroke or cardioembolic stroke.
- Results were broadly consistent in sensitivity analyses using penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches accounting for potential genetic pleiotropy or outliers.
Why it matters
This genetic analysis found that higher genetically predicted lipoprotein(a) levels were associated with increased risk of large artery stroke and with Alzheimer disease. It examines a possible causal risk factor but does not test or show any treatment or prevention.
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Study details
- Participants696
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stroke) |
| Journal's citation record | 3 / 4 | Stroke: journal h-index 455 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 696 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 88 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.8 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 3.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Yongjun Wang: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Capital Medical University: institution h-index 643 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31597550) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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