CoChat
Sign Up
Cited by 49Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsAcute Myocardial Infarction Research

Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome

Open access
Shao, QiaoYu, Yang, ZhiQiang, Wang, YuFei, Li, QiuXuan, Han, KangNing, Liang, Jing, Shen, Hua, Liu, XiaoLi +3 more·2022·Journal of Atherosclerosis and Thrombosis
DOI 10.5551/jat.63397PMC PMC9881534
Open this paper in CoChat — free accountOpen PDF

Abstract

AIMS: This study aimed to investigate the association of elevated RC levels with adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients with and without diabetes. METHODS: We analyzed data from 1716 patients with ACS undergoing percutaneous coronary intervention. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. RC ＞75th percentile of the cohort (＞0.79 mmol/L) was defined as abnormally elevated RC. Cox-regression models and Kaplan-Meier analyses were used to assess the relationship between RC ＞0.79 mmol/L and major adverse cardiovascular events (MACE). RESULTS: During a median follow-up of 927 days, a total of 354 patients had at least one event. In the overall population, compared with those with RC ≤ 0.79 mmol/L, patients with RC ＞0.79 mmol/L had a significantly higher risk of MACE after adjustment for potential confounders (hazard ratio: 1.572, 95% confidence interval: 1.251-1.975, P＜0.001). In addition, RC ＞0.79 mmol/L was associated with an increased risk of MACE of 66.7% (P=0.001) and 50.1% (P=0.022) in the diabetic and non-diabetic subgroups (P for interaction=0.073), respectively. The addition of RC significantly improved the predictive ability of baseline models for MACE in diabetic patients (all P＜0.05), but not in non-diabetic patients (all P＞0.05). CONCLUSION: Abnormally elevated RC was significantly associated with worse prognosis in both diabetic and non-diabetic patients with ACS; however, the prognostic value of RC might be superior among diabetic patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.5551/jat.63397

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • RC is associated with CHD prognosis, with elevated RC levels significantly increasing the risk of cardiovascular events and all-cause mortality in patients with CHD.

    “Current evidence indicates that RC, an emerging lipid marker, is associated with CHD prognosis, with elevated RC levels significantly increasing the risk of cardiovascular events and all-cause mortality in patients with CHD (17–19).”

    From Remnant cholesterol, lipid ratios, and the severity of coronary artery lesions: a retrospective cohort study in patients with coronary heart disease (2025) · cites this paper as [19]

    In Results, Table 3 reports that elevated RC was significantly associated with major adverse cardiovascular events among patients with acute coronary syndrome undergoing PCI (adjusted HR 1.572, P<0.001). It does not support the claimed significant increase in all-cause mortality: the adjusted association was not significant (P=0.477). The study population is also narrower than patients with CHD generally. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 43 · Cited by 49

Research works printed but not linked: 31

  1. [1]Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH and Witztum JL: Lipoprotein Management in Patients With Cardiometabolic Risk. J Am Coll Cardiol, 2008; 51: 1512-1524 18402913
  2. [2]Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen M-R, Tokgözoglu L, Tybjærg-Hansen A and Watts GF: Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J, 2011; 32: 1345-1361 PMC3105250 21531743
  3. [5]Nordestgaard BG and Varbo A: Triglycerides and cardiovascular disease. Lancet, 2014; 384: 626-635 25131982
  4. [6]Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R and Nordestgaard BG: Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol, 2013; 61: 427-436 23265341
  5. [7]Varbo A and Nordestgaard BG: Remnant Cholesterol and Triglyceride-Rich Lipoproteins in Atherosclerosis Progression and Cardiovascular Disease. Arterioscler Thromb Vasc Biol, 2016; 36: 2133-2135 27784698
  6. [9]Libby P: Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J, 2015; 36: 774-776 PMC4471442 25548060
  7. [10]Klempfner R, Erez A, Sagit BZ, Goldenberg I, Fisman E, Kopel E, Shlomo N, Israel A and Tenenbaum A: Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease: Twenty-Two-Year Follow-Up of the Bezafibrate Infarction Prevention Study and Registry. Circ Cardiovasc Qual Outcomes, 2016; 9: 100-108 26957517
  8. [12]Toth PP, Granowitz C, Hull M, Liassou D, Anderson A and Philip S: High Triglycerides Are Associated With Increased Cardiovascular Events, Medical Costs, and Resource Use: A Real-World Administrative Claims Analysis of Statin-Treated Patients With High Residual Cardiovascular Risk. J Am Heart Assoc, 2018; 7: e008740 PMC6201477 30371242
  9. [13]Nichols GA, Philip S, Reynolds K, Granowitz CB and Fazio S: Increased residual cardiovascular risk in patients with diabetes and high versus normal triglycerides despite statin-controlled LDL cholesterol. Diabetes Obes Metab, 2019; 21: 366-371 PMC6587847 30225881
  10. [14]Jørgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG and Tybjærg-Hansen A: Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J, 2013; 34: 1826-1833 23248205
  11. [15]Varbo A, Benn M, Tybjærg-Hansen A and Nordestgaard BG: Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation, 2013; 128: 1298-1309 23926208
  12. [16]Haffner SM, Lehto S, Rönnemaa T, Pyörälä K and Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med, 1998; 339: 229-234 9673301
  13. [19]Koga H, Sugiyama S, Kugiyama K, Fukushima H, Watanabe K, Sakamoto T, Yoshimura M, Jinnouchi H and Ogawa H: Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease. Eur Heart J, 2006; 27: 817-823 16434416
  14. [20]Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AFH, Stroes E, Taskinen M-R and Tybjærg-Hansen A: Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J, 2013; 34: 3478-3390a PMC3844152 23956253
  15. [22]Castañer O, Pintó X, Subirana I, Amor AJ, Ros E, Hernáez Á, Martínez-González MÁ, Corella D, Salas-Salvadó J, Estruch R, Lapetra J, Gómez-Gracia E, Alonso-Gomez AM, Fiol M, Serra-Majem L, Corbella E, Benaiges D, Sorli JV, Ruiz-Canela M, Babió N, Sierra LT, Ortega E and Fitó M: Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease. J Am Coll Cardiol, 2020; 76: 2712-2724 33272365
  16. [23]Helgadottir A, Gretarsdottir S, Thorleifsson G, Hjartarson E, Sigurdsson A, Magnusdottir A, Jonasdottir A, Kristjansson H, Sulem P, Oddsson A, Sveinbjornsson G, Steinthorsdottir V, Rafnar T, Masson G, Jonsdottir I, Olafsson I, Eyjolfsson GI, Sigurdardottir O, Daneshpour MS, Khalili D, Azizi F, Swinkels DW, Kiemeney L, Quyyumi AA, Levey AI, Patel RS, Hayek SS, Gudmundsdottir IJ, Thorgeirsson G, Thorsteinsdottir U, Gudbjartsson DF, Holm H and Stefansson K: Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease. Nature genetics, 2016; 48: 634-639 PMC9136713 27135400
  17. [24]Varbo A, Freiberg JJ and Nordestgaard BG: Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population. Clin Chem, 2015; 61: 533-543 25605681
  18. [25]Elshazly MB, Mani P, Nissen S, Brennan DM, Clark D, Martin S, Jones SR, Quispe R, Donnellan E, Nicholls SJ and Puri R: Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease. Eur J Prev Cardiol, 2020; 27: 1091-1100 31744333
  19. [27]Twickler TB, Dallinga-Thie GM, Cohn JS and Chapman MJ: Elevated remnant-like particle cholesterol concentration: a characteristic feature of the atherogenic lipoprotein phenotype. Circulation, 2004; 109: 1918-1925 15117861
  20. [28]Prenner SB, Mulvey CK, Ferguson JF, Rickels MR, Bhatt AB and Reilly MP: Very low density lipoprotein cholesterol associates with coronary artery calcification in type 2 diabetes beyond circulating levels of triglycerides. Atherosclerosis, 2014; 236: 244-250 PMC4209900 25105581
  21. [29]Schaefer EJ, McNamara JR, Shah PK, Nakajima K, Cupples LA, Ordovas JM and Wilson PWF: Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study. Diabetes Care, 2002; 25: 989-994 12032104
  22. [30]Puig-Jové C, Castelblanco E, Falguera M, Hernández M, Soldevila B, Julián MT, Teis A, Julve J, Barranco-Altirriba M, Franch-Nadal J, Puig-Domingo M, Ortega E, Amigó N, Alonso N and Mauricio D: Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism. Rev Esp Cardiol (Engl Ed), 2021; 33785266
  23. [31]Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL and Liao Y: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes, 2003; 52: 453-462 12540621
  24. [32]Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, Siscovick D, Freedman DS and Kronmal R: Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. Arterioscler Thromb Vasc Biol, 2002; 22: 1175-1180 12117734
  25. [33]Grundy SM and Vega GL: Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Implications for treatment. Arch Intern Med, 1992; 152: 28-34 1728925
  26. [34]Tani S, Yagi T, Atsumi W, Kawauchi K, Matsuo R and Hirayama A: Relation between low-density lipoprotein cholesterol/apolipoprotein B ratio and triglyceride-rich lipoproteins in patients with coronary artery disease and type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol, 2017; 16: 123 PMC5625702 28969633
  27. [36]Feng X, Guo Q, Zhou S, Sun T, Liu Y, Zhou Z and Zhou Y: Could remnant-like particle cholesterol become a risk factor in diabetic menopausal women with coronary artery disease? A cross-sectional study of single academic center in China. Lipids Health Dis, 2020; 19: 44 PMC7076918 32178671
  28. [37]Zhao Q, Zhang T-Y, Cheng Y-J, Ma Y, Xu Y-K, Yang J-Q and Zhou Y-J: Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China. Lipids Health Dis, 2020; 19: 179 PMC7393817 32736631
  29. [38]Quispe R, Martin SS, Michos ED, Lamba I, Blumenthal RS, Saeed A, Lima J, Puri R, Nomura S, Tsai M, Wilkins J, Ballantyne CM, Nicholls S, Jones SR and Elshazly MB: Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. Eur Heart J, 2021; 42: 4324-4332 PMC8572557 34293083
  30. [39]Vallejo-Vaz AJ, Fayyad R, Boekholdt SM, Hovingh GK, Kastelein JJ, Melamed S, Barter P, Waters DD and Ray KK: Triglyceride-Rich Lipoprotein Cholesterol and Risk of Cardiovascular Events Among Patients Receiving Statin Therapy in the TNT Trial. Circulation, 2018; 138: 770-781 29618599
  31. [40]Cao Y-X, Zhang H-W, Jin J-L, Liu H-H, Zhang Y, Gao Y, Guo Y-L, Wu N-Q, Hua Q, Li Y-F, Li X-L, Xu R-X, Cui C-J, Liu G, Dong Q, Sun J, Zhu C-G and Li J-J: The longitudinal association of remnant cholesterol with cardiovascular outcomes in patients with diabetes and pre-diabetes. Cardiovasc Diabetol, 2020; 19: 104 PMC7339517 32631321

Authors
Shao, Q., Yang, Z., Wang, Y., Li, Q., Han, K., Liang, J., Shen, H., Liu, X., Zhou, Y., Ma, X., & Wang, Z.
Affiliations
  • Capital Medical University (CN)
  • Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University
ORCID
Venue
Journal of Atherosclerosis and Thrombosis
Publisher
Japan Atherosclerosis Society
Published
2022-12-01
Volume
29
Issue
12
Pages
1808-1822
ISSN
  • 1340-3478 (ISSN-L)
  • 1880-3873
DOI
10.5551/jat.63397
PMC
PMC9881534
OpenAlex
W4213414427
Cited by
49
References
43
Citations by year
2026: 10 · 2025: 7 · 2024: 11 · 2023: 16 · 2022: 5
FWCI
9.32
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Journal of Atherosclerosis and Thrombosis (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • China Postdoctoral Science Foundation (SML20180601, 2021-ZZ-023, 2017YFC0908800, 2021M692253)
  • Beijing Postdoctoral Science Foundation (2017YFC0908800, 2021M692253, SML20180601, 2021‐ZZ‐023)
  • Beijing Municipal Health Commission (2017YFC0908800, SML20180601)
  • Beijing Municipal Administration of Hospitals (2017YFC0908800, SML20180601)
  • National Key Research and Development Program of China (2021-ZZ-023, 2017YFC 0908800, 2021M692253, SML20180601)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords
remnant cholesterol, acute coronary syndrome, major adverse cardiovascular events, diabetes mellitus, percutaneous coronary intervention, prognostic factors, cardiovascular risk prediction
MeSH terms
Diabetes Mellitus, Humans, Hypercholesterolemia, Cholesterol, HDL, Cholesterol, LDL, Risk Factors, Proportional Hazards Models, Acute Coronary Syndrome, Percutaneous Coronary Intervention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review