Remnant Cholesterol and the Risk of Coronary Artery Calcium Progression: Insights From the CARDIA and MESA Study
Abstract
Background: Remnant cholesterol (RC) contributes to residual risk of atherosclerotic cardiovascular disease, but population-based evidence on the prospective relationship between RC and coronary artery calcium (CAC) progression is rare. Methods: We pooled data obtained from 6544 atherosclerotic cardiovascular disease–free individuals from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=2635) and MESA (Multi-Ethnic Study of Atherosclerosis; n=3909), with a mean±SD age of 47.2±19.8 years; 3019 (46.1%) were men who completed computed tomography of CAC at baseline. RC was measured as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus calculated LDL (low-density lipoprotein) cholesterol (LDL-C) estimated by using the Martin/Hopkins equation. Adjusted Cox models were used to assess the relationships between RC levels and CAC progression. We also performed discordance analyses examining the risk of CAC progression in RC versus LDL-C discordant/concordant groups using median cut points and clinically relevant LDL-C targets. Results: During a median follow-up of 8.6 years, 2778 (42.5%) participants had CAC progression. After multivariable adjustment for demographics and cardiovascular risk factors, a 1-mg/dL increase in RC levels was associated with a 1.3% higher risk of CAC progression (hazard ratio, 1.013 [95% CI, 1.008–1.017]). Results were similar when we categorized individuals by RC quartiles. Furthermore, the discordant high RC/low LDL-C group had a significantly higher risk of CAC progression than the concordant low RC/LDL-C group regarding their medians (hazard ratio, 1.195 [95% CI, 1.063–1.343]) or when setting the clinical LDL-C cut points at 100 and 130 but not 70 mg/dL. The association remained robust across a series of sensitivity analyses. Conclusions: Elevated RC levels were associated with an increased risk of CAC progression independent of traditional cardiovascular risk factors, even in individuals with optimal LDL-C levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00005130 (CARDIA) and NCT00005487 (MESA).
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Higher remnant lipoprotein cholesterol is independently associated with coronary artery calcium progression even when LDL-C is optimal.
“Moreover, higher remnant lipoprotein cholesterol is independently associated with CAC progression even when LDL-C is optimal, supporting a link between TRL remnants and calcific atherosclerosis [31].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [31]
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“In a prospective study involving 6,544 individuals without atherosclerotic cardiovascular disease (ASCVD), RC levels were closely associated with the severity of coronary artery calci fi cation, a relationship that remained signi fi cant even in patients with well-controlled LDL-C levels (28).”
Alam, U., Mathai, S. V., Filtz, A., Kuno, T., Badimon, J. J., Sniderman, A. D., Virani, S. S., Toth, P. P., Shapiro, M. D., Lavie, C. J., et al. (2026) · Current Cardiology Reports · doi:10.1007/s11886-025-02337-1 · Cited by 4 · see citing works
- Authors
- Hao, Q.-Y., Gao, J.-W., Yuan, Z.-M., Gao, M., Wang, J.-F., Schiele, F., Zhang, S.-L., & Liu, P.-M.
- Affiliations
- Sun Yat-sen University (CN)
- Department of Clinical Nutrition (Z.-M.Y.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
- Department of Cardiology (Q.-Y.H., J.-W.G., J.-F.W., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
- Centre Hospitalier Universitaire de Besançon (FR)
- Corresponding author
- Hao, Qing-Yun
- Gao, Jing-Wei
- Venue
- Circulation: Cardiovascular Imaging
- Published
- 2022-07
- Volume
- 15
- Issue
- 7
- Pages
- e014116-e014116
- ISSN
- 1941-9651 (ISSN-L)
- 1942-0080
- OpenAlex
- W4284882729
- Cited by
- 49
- References
- 5
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 16 · 2023: 5 · 2022: 2
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Cardiovascular Imaging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81870315)
- National Heart, Lung, and Blood Institute (HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, HHSN268201800007I, HHSN268201800003I)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- remnant cholesterol, coronary artery calcium progression, atherosclerotic cardiovascular disease, LDL cholesterol, residual cardiovascular risk, young adults, cardiovascular risk factors, LDL cholesterol targets, gastric cardia, MESA, CT calcium scoring, Martin-Hopkins equation, HDL cholesterol, LDL cholesterol estimation, cardiovascular risk prediction models, coronary artery calcification, coronary artery disease risk
- MeSH terms
- Adult, Aged, Calcium, Cholesterol, Coronary Artery Disease, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Prospective Studies, Risk Factors, Atherosclerosis
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