The atherogenic dyslipidemia complex and novel approaches to cardiovascular disease prevention in diabetes

Stahel, Priska; Xiao, Changting; Hegele, Robert A.; Lewis, Gary F.

doi:10.1016/j.cjca.2017.12.007

Cited by 76Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsLipid metabolism and disorders

The atherogenic dyslipidemia complex and novel approaches to cardiovascular disease prevention in diabetes

Stahel, Priska, Xiao, Changting, Hegele, Robert A., Lewis, Gary F.·2018·Canadian Journal of Cardiology

DOI 10.1016/j.cjca.2017.12.007

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Abstract

Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic cardiovascular disease remains. Residual risk might in part be explained by lipid abnormalities that go beyond LDL cholesterol elevation, collectively termed the "atherogenic dyslipidemia complex (ADC)," consisting of hypertriglyceridemia, elevated small dense LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia. In this review, we briefly discuss the pathophysiology of the typical dyslipidemia that occurs in insulin-resistant states including obesity, the metabolic syndrome, and type 2 diabetes. Lipid-modifying strategies including lifestyle modification, ezetimibe, statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors in treating ADC are discussed. With the advent of novel therapies involving antisense oligonucleotides and monoclonal antibodies, new targets can be specifically downregulated to potentially promote lipoprotein clearance or suppress production. We review novel approaches currently undergoing clinical testing and we speculate on their suitability for use in treating ADC for the prevention of atherosclerotic cardiovascular disease. In addition, future targets that might be considered for therapeutic development are discussed.

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Apo C-III inhibits removal of remnants; in states of increased VLDL secretion with elevated apo C-III, uptake of remnant particles is reduced, compounding dyslipidaemia.
“Also, apo C-III inhibits removal of remnants; thus in states of increased VLDL secretion, when apo C-III is elevated, uptake of remnant particles will be reduced, compounding the dyslipidaemia.16”
From Clinical review on triglycerides (2020) · cites this paper as [16]

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The pro-inflammatory marker soluble suppression of tumorigenicity-2 (ST2) is reduced especially in diabetic morbidly obese patients undergoing bariatric surgery
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Changes over time in the cardiovascular risk profile of type 2 diabetes from 2007 to 2020: A community‐based study
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Koroner yavaş akım fenomeni olan hastalarda plazma aterojenik indeksinin incelenmesi.
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Additional file 3 of Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis
Guan, B., Wang, A., & Xu, H. (2023) · Figshare · doi:10.6084/m9.figshare.23930438
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Additional file 2 of Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis
Guan, B., Wang, A., & Xu, H. (2023) · Figshare · doi:10.6084/m9.figshare.23930435
Additional file 1 of Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis
Guan, B., Wang, A., & Xu, H. (2023) · Figshare · doi:10.6084/m9.figshare.23930429
Additional file 2 of Non-linear association of atherogenic index of plasma with bone mineral density a cross-sectional study
Xu, B., Ma, G., Yang, L., Chen, X., Bian, B., Yang, B., Zhang, D., Qin, X., Zhu, L., Yin, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26027666
Additional file 1 of Non-linear association of atherogenic index of plasma with bone mineral density a cross-sectional study
Xu, B., Ma, G., Yang, L., Chen, X., Bian, B., Yang, B., Zhang, D., Qin, X., Zhu, L., Yin, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26027594
Additional file 1 of Non-linear association of atherogenic index of plasma with insulin resistance and type 2 diabetes: a cross-sectional study
Yin, B., Wu, Z., Xia, Y., Xiao, S., Chen, L., & Li, Y. (2023) · Figshare · doi:10.6084/m9.figshare.23606971

Pharmacological targeting of the atherogenic dyslipidemia complex: the next frontier in CVD prevention beyond lowering LDL cholesterol
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Authors: Stahel, P., Xiao, C., Hegele, R. A., & Lewis, G. F.
Affiliations: University of Toronto (CA)
Western University (CA)
Corresponding author: Lewis, Gary F.
ORCID: Stahel, Priska
Xiao, Changting
Hegele, Robert A.
Lewis, Gary F.
Venue: Canadian Journal of Cardiology
Publisher: Elsevier BV
Published: 2018-05
Volume: 34
Issue: 5
Pages: 595-604
ISSN: 0828-282X (ISSN-L)
DOI: 10.1016/j.cjca.2017.12.007
OpenAlex: W2774613779
Cited by: 75
References: 84
Citations by year: 2026: 1 · 2025: 7 · 2024: 9 · 2023: 15 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 10
FWCI: 1.45
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Canadian Journal of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
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 › Lipid metabolism and disorders
Keywords: diabetic dyslipidemia, atherosclerotic cardiovascular disease prevention, residual cardiovascular risk, hypertriglyceridemia, small dense LDL, remnant lipoproteins, postprandial lipemia, HDL cholesterol, insulin resistance, metabolic syndrome, obesity, ezetimibe, statins, fibrates, nicotinic acid, cholesteryl ester transfer protein inhibitors, antisense oligonucleotides, monoclonal antibodies, lipoprotein clearance, type 2 diabetes
MeSH terms: Drug Development, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Patient Care Management, Dyslipidemias, Atherosclerosis

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The atherogenic dyslipidemia complex and novel approaches to cardiovascular disease prevention in diabetes

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