Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C
Abstract
AIMS: Analyses using conventional statistical methodologies have yielded conflicting results as to whether low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) is the best marker of the apoB-associated risk of coronary heart disease. The aim of this study was to determine the additional value of apoB beyond LDL-C or non-HDL-C as a predictor of coronary heart disease. METHODS AND RESULTS: For each patient from the Framingham Offspring Cohort aged 40-75 years (n = 2966), we calculated the extent to which the observed apoB differed from the expected apoB based on their LDL-C or non-HDL-C. We added this difference to a Cox model predicting new onset coronary heart disease over a maximum of 20 years adjusting for standard risk factors plus LDL-C or non-HDL. The difference between observed and expected apoB over LDL-C or non-HDL-C was highly prognostic of future coronary heart disease events: adjusted hazard ratios 1.26 (95% confidence interval: 1.15, 1.37) and 1.20 (1.11, 1.29), respectively, for each standard deviation increase beyond expected apoB levels. When this difference between observed and expected apoB was added to standard coronary heart disease prediction models including LDL-C or non-HDL-C, prediction improved significantly (likelihood ratio test p-values <0.0001) and discrimination c-statistics increased from 0.72 to 0.73. The corresponding relative integrated discrimination improvements were 11% and 8%, respectively. CONCLUSIONS: apoB improves risk assessment of future coronary heart disease events over and beyond LDL-C or non-HDL-C, which is consistent with coronary risk being more closely related to the number of atherogenic apoB particles than to the mass of cholesterol within them.
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All reports since 2019, with one exception, including observational studies and randomized clinical trials, have confirmed that apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C.
“Moreover, all reports since then, with one exception,2 including observational studies and randomized clinical trials,3–13 have confirmed that apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C, reinforcing the validity of the evaluation by the 2019 EAS/ESC Guidelines as to the superiority of apoB.”
From Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention (2024) · cites this paper as [8]
apoB is a more accurate measure of the adequacy of lipid-lowering therapy than LDL-C or non-HDL-C.
“given that apoB is a more accurate measure of the adequacy of lipid-lowering therapy than LDL-C or non-HDL-C,1,3–13,27”
From Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention (2024) · cites this paper as [8]
A high apolipoprotein B (apo B) level is a risk factor for ASCVD.
“A high apolipoprotein B (apo B) level is a risk factor for ASCVD. (Evidence level: E-1a)”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [269]
Apo B is a stronger risk factor for cardiovascular events than are LDL-C and HDL-C.
“According to a meta-analysis of epidemiological studies, apo B is a stronger risk factor for cardiovascular events than are LDL-C and HDL-C268, 269).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [269]
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Self-citation
- Authors
- Pencina, M. J., D’Agostino, R. B., Zdrojewski, T., Williams, K., Thanassoulis, G., Furberg, C. D., Peterson, E. D., Vasan, R. S., & Sniderman, A. D.
- Affiliations
- Duke University (US)
- Boston University (US)
- Gdańsk Medical University (PL)
- KenAnCo Biostatistics, San Antonio, USA
- McGill University Health Centre (CA)
- Wake Forest University Health Sciences (US)
- Duke Medical Center (US)
- Framingham Heart Study (US)
- Royal Victoria Hospital (CA)
- Corresponding author
- Pencina, Michael J
- ORCID
- Venue
- European Journal of Preventive Cardiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-01-29
- Volume
- 22
- Issue
- 10
- Pages
- 1321-1327
- ISSN
- 2047-4873 (ISSN-L)
- 2047-4881
- OpenAlex
- W1984970871
- Cited by
- 164
- References
- 27
- Citations by year
- 2026: 19 · 2025: 12 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 13 · 2020: 9 · 2019: 16 · 2018: 17 · 2017: 11 · 2016: 13 · 2015: 6
- FWCI
- 15.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Preventive Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Heart, Lung, and Blood Institute (N01‐HC25195)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein B, coronary heart disease risk prediction, LDL cholesterol, non-HDL cholesterol, Framingham Offspring cohort, cardiovascular risk assessment
- MeSH terms
- Adult, Aged, Cholesterol, Coronary Disease, Decision Support Techniques, Female, Humans, Cholesterol, LDL, Male, Massachusetts, Middle Aged, Predictive Value of Tests, Risk Factors, Time Factors, Biomarkers, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Disease-Free Survival, Dyslipidemias, Kaplan-Meier Estimate, Apolipoprotein B-100
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