Plasma levels of apolipoprotein E and risk of ischemic heart disease in the general population
Abstract
Background and aims Triglyceride-rich lipoproteins are causally associated with high risk of ischemic heart disease (IHD), and apolipoprotein E (apoE) has a central role in their plasma clearance. While both quantitative and qualitative changes of apoE are established causes of rare dyslipidemia syndromes, it remains unclear whether plasma levels of apoE are associated with risk of IHD in the general population. Methods We tested whether plasma levels of apoE at enrollment were associated with future risk of IHD and myocardial infarction (MI) in 91,695 individuals from the general population. Results Multifactorially adjusted hazard ratios (HRs) for highest versus lowest apoE tertile were 1.15 (1.04-1.27) for IHD and 1.16 (1.00-1.36) for MI in men, and 0.94 (0.84-1.05) and 1.04 (0.85-1.26) in women. These associations were attenuated by adjustments for triglyceride levels. Corresponding HRs for highest versus lowest apoE tertile in ε33 carriers were 1.18 (1.03-1.36) for IHD and 1.21 (0.98-1.49) for MI in men, and 0.91 (0.78-1.06) and 0.93 (0.71-1.21) in women. Thus, the present associations were independent of APOE genotype. Conclusion These findings suggest that high plasma levels of apoE are associated with IHD in men but not in women. Triglyceride-rich lipoproteins may partly explain these associations.
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In analyses stratified by APOE genotype and gender, LDL cholesterol, HDL cholesterol, triglycerides, apoA1 and apoB vary with plasma levels of apoE.
“Furthermore, it has been shown, in analyses stratified by APOE genotype and gender, that LDL cholesterol, HDL cholesterol, triglycerides, apoA1 and apoB vary with plasma levels of apoE [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
In the cohort of about 91,000 participants, the association between high plasma apoE and risk of ischemic heart disease was not attenuated after adjustment for APOE genotype or stratification by ε33 genotype.
“In this study, the epidemiological association between high plasma levels of apoE and risk of ischemic heart disease was not attenuated after adjustment for APOE genotype or after stratification by ε33 genotype, emphasizing a quantitative importance of apoE [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
High plasma levels of apoE seem to be associated with increased risk of ischemic heart disease, an association possibly mediated by triglyceride-rich lipoproteins.
“Taken together, high plasma levels of apoE seems to be associated with increased risk of ischemic heart disease, an association possibly mediated by triglyceride-rich lipoproteins [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
Triglycerides most likely mediate the association between high plasma apoE and risk of ischemic heart disease.
“reflecting that triglycerides most likely mediate these observations [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
In the cohort of about 91,000 participants, the associations between high plasma apoE and risk of ischemic heart disease were attenuated after adjustment for levels of triglycerides.
“However, the associations were attenuated after adjustment for levels of triglycerides, reflecting that triglycerides most likely mediate these observations [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
In a prospective general population cohort of about 91,000 participants, high plasma levels of apoE were associated with increased risk of ischemic heart disease in men but not in women.
“In a prospective general population cohort study with ~91,000 participants, high plasma levels of apoE were associated with increased risk of ischemic heart disease in men but not in women [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
Rasmussen et al. showed that adjustment for C-reactive protein did not have any impact on the risk between plasma levels of apoE and ischemic heart disease.
“The importance of high C-reactive protein levels has been investigated by some studies, however Rasmussen et al. showed that adjustment for C-reactive protein did not have any impact on the risk between plasma levels of apoE and ischemic heart disease [44,116,121,122].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
The general population cohort of about 91,000 individuals covers ages from 20 to 100+ years and shows strong associations between all major lipids, lipoproteins and apolipoproteins and risk of ischemic heart disease.
“In contrast, the general population cohort of ~91,000 individuals covers ages from 20 to 100þ years, and shows strong associations between all major lipids, lipoproteins and apolipoproteins and risk of ischemic heart disease [116].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [116]
High levels of plasma apoE have been reported to be associated with increased risk of ischaemic heart disease.
“Interestingly, low levels of plasma apoE were recently reported to be associated with increased risk of dementia,17,23,24 whereas high levels were associated with increased risk of ischaemic heart disease.25”
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- Authors
- Rasmussen, K. L., Tybjærg-Hansen, A., Nordestgaard, B. G., & Frikke-Schmidt, R.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Rasmussen, Katrine L.
- Nordestgaard, Børge G.
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 246
- Pages
- 63-70
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2210383430
- Cited by
- 47
- References
- 40
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 4
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Lundbeckfonden (R126-2012-12556, R211-2015-3977)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- apolipoprotein E, ischemic heart disease, myocardial infarction, triglyceride-rich lipoproteins, APOE genotype, sex differences, triglyceride levels, cardiovascular risk
- MeSH terms
- Aged, Apolipoproteins E, Denmark, Female, Genotype, Humans, Male, Middle Aged, Myocardial Infarction, Phenotype, Prospective Studies, Risk Factors, Time Factors, Triglycerides, Biomarkers, Multivariate Analysis, Chi-Square Distribution, Linear Models, Logistic Models, Proportional Hazards Models, Myocardial Ischemia, Risk Assessment, Kaplan-Meier Estimate
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