SynthesisInternational journal of epidemiology2013
Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals.
Synthesis in International journal of epidemiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 11 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 11 syntheses or guidelines pooled it, 172 citations in OpenAlex.
- Association of apolipoprotein E polymorphisms (E2, E3, E4) with type 2 diabetes: a meta-analysis of case-control studies.The Pan African medical journal · 2026Pooled it
- Unraveling Mechanisms of Cryptogenic Stroke at the Genetic Level: A Systematic Literature Review.Journal of the American Heart Association · 2023Pooled it
- Apolipoprotein EDisease markers · 2022Pooled it
- Can Physical Activity Reduce the Risk of Cognitive Decline in Apolipoprotein e4 Carriers? A Systematic Review.International journal of environmental research and public health · 2021Pooled it
- Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2021Pooled it
- Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank.EBioMedicine · 2020Pooled it
- The Role of DNA Methylation in Ischemic Stroke: A Systematic Review.Frontiers in neurology · 2020Pooled it
- Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.International journal of epidemiology · 2016Pooled it
- Pooled it
- Pooled it
- Prognostic value of apolipoproteins in COVID-19 patients: A systematic review and meta-analysis.Travel medicine and infectious diseasePooled it
- Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease.The journal of prevention of Alzheimer's disease · 2026Trial
- Apolipoprotein E Plasma Concentrations Are Predictive of Recurrent Strokes: Insights From the SPARCL Trial.Journal of the American Heart Association · 2025Trial
- Trial
- Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women.The American journal of cardiology · 2019Trial
- Apolipoprotein E4 genotype in combination with poor metabolic profile is associated with reduced cognitive performance in healthy postmenopausal women: implications for late onset Alzheimer's disease.Menopause (New York, N.Y.) · 2019Trial
- Trial
- APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome.Scientific reports · 2017Trial
- Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar inuit populations.Circulation. Cardiovascular genetics · 2015Trial
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
49 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAt the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
methodsWe conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60,883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).
resultsThe ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.
conclusionsIn people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.