Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: A primary prevention study
Open accessAbstract
Aims: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. Methods and results: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints. Conclusions: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
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Elevated levels of cholesterol-enriched remnant lipoproteins contribute to the development of premature coronary and peripheral atherosclerosis.
“As a result, elevated levels of cholesterol-enriched remnant lipoproteins contribute to the development of premature coronary [22,23,24] and peripheral [25,26] atherosclerosis.”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [23]
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- Authors
- Quispe, R., Martin, S. S., Michos, E. D., Lamba, I., Blumenthal, R. S., Saeed, A., Lima, J., Puri, R., Nomura, S., Tsai, M., Wilkins, J., Ballantyne, C. M., Nicholls, S., Jones, S. R., & Elshazly, M. B.
- Affiliations
- Johns Hopkins University (US)
- NewYork–Presbyterian Hospital (US)
- University of Pittsburgh Medical Center (US)
- Division of Cardiology, Johns Hopkins University School of Medicine , Baltimore, MD, USA
- Cleveland Clinic (US)
- University of Minnesota (US)
- Northwestern University (US)
- Houston Methodist (US)
- Monash University (AU)
- Corresponding author
- Elshazly, Mohamed Badreldin
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-07-19
- Volume
- 42
- Issue
- 42
- Pages
- 4324-4332
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC8572557
- OpenAlex
- W3185962386
- Cited by
- 441
- References
- 23
- Citations by year
- 2026: 76 · 2025: 117 · 2024: 117 · 2023: 76 · 2022: 45 · 2021: 8
- FWCI
- 57.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- European Heart Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (5T32HL007227)
- National Heart, Lung, and Blood Institute (UL1-TR-000040, UL1-TR-001079, UL1-TR-001420)
- National Institutes of Health
- Department of Health and Human Services (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I)
- National Center for Advancing Translational Sciences
- University of Alabama at Birmingham (HHSN268201300025C, HHSN268201300026C)
- Northwestern University (HHSN268201300027C)
- University of Minnesota (HHSN268201300028C)
- Kaiser Foundation Research Institute (HHSN268201300029C)
- Johns Hopkins University School of Medicine (HHSN268200900041C)
- National Institute on Aging
- 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
- remnant cholesterol, atherosclerotic cardiovascular disease, LDL cholesterol, apolipoprotein B, non-HDL cholesterol, primary prevention, cardiovascular risk prediction, incident cardiovascular events
- MeSH terms
- Adult, Aged, Apolipoproteins B, Cardiovascular Diseases, Cholesterol, Female, Humans, Cholesterol, HDL, Middle Aged, Primary Prevention, Prospective Studies, Risk Factors
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