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Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events
Open accessAbstract
Objectives—: Non–high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume. Approach and Results—: Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) </≥70 mg/dL and C-reactive protein </≥2 mg/L and in patients with or without diabetes mellitus. On-treatment non-HDLC levels linearly associated with ΔPAV. Overt PAV progression (ΔPAV>0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status ( P <0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (β=0.62; P <0.001) compared with changes in LDLC (β=0.51; P <0.001). Kaplan–Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve. Conclusions—: Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk.
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“Elevated levels of TRLs and remnant lipoproteins contribute directly to atherosclerosis by promoting endothelial dysfunction, inflammation, and foam cell formation [8, 9].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [9]
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“Genetic studies and epidemiologic data increasingly implicate remnant lipoproteins as causal contributors to atherogenesis, providing a strong mechanistic and clinical rationale for targeted intervention [8–12].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [9]
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Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease
Castañer, O., Pintó, X., Subirana, I., Amor, A. J., Ros, E., Hernáez, Á., Martínez-González, M. Á., Corella, D., Salas-Salvadó, J., Estruch, R., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.10.008 · Cited by 540
“Our results confirmed previous evidence on the causal role of triglycerides in CVD (7,8,10,26).”
ResultHypertriglyceridaemia and risk of coronary artery disease
Reiner, Ž. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.31 · Cited by 390
Kwaifa, I. K., Bahari, H., Yong, Y. K., & Noor, S. M. (2020) · Biomolecules · doi:10.3390/biom10020291 · Cited by 345
“Other related biomarkers include: growth differentiation factor-15 (GDF15), myeloid-related proteins 8/14, pentraxin 3, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which were identified as surrogate markers of atherosclerosis associated with cardiovascular diseases during obesity [45,46], whil…”
BackgroundHypertriglyceridemia and atherosclerosis
Peng, J., Luo, F., Ruan, G., Peng, R., & Li, X. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0625-0 · Cited by 268
“[32] analyzed the data from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to measure coronary atheroma volume and investigated the relationship between achieved non-HDLC and TG levels with coronary atheroma progression regression rates in a large cohort…”
MethodNicholls, S. J., Lincoff, A. M., Bash, D., Ballantyne, C. M., Barter, P. J., Davidson, M. H., Kastelein, J. J. P., Koenig, W., McGuire, D. K., Mozaffarian, D., et al. (2018) · Clinical Cardiology · doi:10.1002/clc.23055 · Cited by 167
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Metadata
- Authors
- Puri, R., Nissen, S. E., Shao, M., Elshazly, M. B., Kataoka, Y., Kapadia, S. R., Tuzcu, E. M., & Nicholls, S. J.
- Affiliations
- Cleveland Clinic (US)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2016-11
- Volume
- 36
- Issue
- 11
- Pages
- 2220-2228
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2509381650
- Cited by
- 143
- References
- 46
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 17 · 2023: 18 · 2022: 8 · 2021: 11 · 2020: 17 · 2019: 24 · 2018: 20 · 2017: 14 · 2016: 3
- FWCI
- 22.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Sanofi
- Cleveland Clinic
- InfraRedx
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
- Keywords
- non-HDL cholesterol, triglycerides, atherosclerosis progression, LDL cholesterol, triglyceride-rich lipoproteins, residual cardiovascular risk, major adverse cardiovascular events, intravascular ultrasound, coronary artery disease, diabetes mellitus, C-reactive protein
- MeSH terms
- Aged, Hypolipidemic Agents, Cholesterol, Clinical Trials as Topic, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Time Factors, Triglycerides, Biomarkers, Multivariate Analysis, Linear Models, Treatment Outcome, Ultrasonography, Interventional, Disease Progression, Kaplan-Meier Estimate, Plaque, Atherosclerotic
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