Highlights
- •A low EPA/AA ratio is related to more vulnerable properties in nonculprit plaques.
- •The association is also demonstrated among patients with an LDL-C < 100mg/dL.
- •Low EPA/AA and high LDL-C levels are associated with more TCFA in nonculprit plaques.
- •Our results suggest the pathogenesis of recurrent events in cases of low EPA/AA.
Abstract
Background
A low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an
increased risk of cardiovascular events in patients with coronary artery disease (CAD).
Objective
To clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary
plaques in statin-treated patients with CAD.
Methods
A total of 370 consecutive stable coronary disease patients treated with statins,
who underwent percutaneous coronary intervention for the culprit lesion and optical
coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were
included. The characteristics of non-culprit plaques assessed using OCT were compared
between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group
(EPA/AA ≥0.4, n = 115).
Results
The prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA
group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence
of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and
higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL)
(odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of
lipid-rich plaque, plaque with macrophages, and cholesterol crystals.
Conclusion
Lower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics
in non-culprit plaques. The present results suggest the importance of EPA/AA ratio
on the secondary prevention of CAD.
Graphical abstract
Graphical Abstract
Keywords
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References
- Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention.Circ J. 2012; 76: 423-429https://doi.org/10.1253/circj.CJ-11-0941
- Significance of imbalance in the ratio of serum n-3 to n-6 polyunsaturated fatty acids in patients with acute coronary syndrome.Am J Cardiol. 2014; 113: 441-445https://doi.org/10.1016/j.amjcard.2013.10.011
- Fish oil fatty acids and human platelets: Dose-dependent decrease in dienoic and increase in trienoic thromboxane generation.Biochem Pharmacol. 1996; 52: 1211-1217https://doi.org/10.1016/0006-2952(96)00473-X
- Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome.Diabetes Care. 2007; 30: 144-146https://doi.org/10.2337/dc06-1179
- Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: A randomised controlled trial.Lancet. 2003; 361: 477-485https://doi.org/10.1016/S0140-6736(03)12468-3
- Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans.Lipids. 1997; 32: 435-439https://doi.org/10.1007/s11745-997-0057-5
- Arachidonate 5-Lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.N Engl J Med. 2004; 350: 29-37https://doi.org/10.1056/nejmoa025079
- Low eicosapentaenoic acid to arachidonic acid ratio is associated with thin-cap fibroatheroma determined by optical coherence tomography.J Cardiol. 2015; 66: 482-488https://doi.org/10.1016/j.jjcc.2015.01.008
- Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study.Heart Vessels. 2014; 29: 596-602https://doi.org/10.1007/s00380-013-0404-4
- Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease - Secondary prevention analysis from JELIS.Circ J. 2009; 73: 1283-1290https://doi.org/10.1253/circj.CJ-08-1197
- Simultaneous evaluation of fatty acid and triglycerides after percutaneous coronary intervention.J Cardiol. 2022; 80: 149-154https://doi.org/10.1016/j.jjcc.2022.02.011
- Prognostic impact of healed coronary plaque in non-culprit lesions assessed by optical coherence tomography.Atherosclerosis. 2020; 309: 1-7https://doi.org/10.1016/j.atherosclerosis.2020.07.005
- Optical coherence tomography in coronary atherosclerosis assessment and intervention.Nat Rev Cardiol. 2022; (Published online): 1-2https://doi.org/10.1038/s41569-022-00687-9
- Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: A report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.J Am Coll Cardiol. 2012; 59: 1058-1072https://doi.org/10.1016/j.jacc.2011.09.079
- Serial 3-vessel optical coherence tomography and intravascular ultrasound analysis of changing morphologies associated with lesion progression in patients with stable angina pectoris.Circ Cardiovasc Imaging. 2017; 10: 1-9https://doi.org/10.1161/CIRCIMAGING.117.006347
- Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease.Am J Cardiol. 2010; 105: 1673-1678https://doi.org/10.1016/j.amjcard.2010.01.346
- Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography.Nat Med. 2011; 17: 1010-1014https://doi.org/10.1038/nm.2409
- JCS 2018 guideline on diagnosis of chronic coronary heart diseases.Circ J. 2021; 85: 402-572https://doi.org/10.1253/CIRCJ.CJ-19-1131
- Incidence, factors, and clinical significance of cholesterol crystals in coronary plaque: An optical coherence tomography study.Atherosclerosis. 2019; 283: 79-84https://doi.org/10.1016/j.atherosclerosis.2019.02.009
- A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.J Cardiol. 2017; 70: 537-544https://doi.org/10.1016/j.jjcc.2017.07.007
- Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in patients with coronary atherosclerotic plaque: An optical coherence tomography study.J Atheroscler Thromb. 2015; 22: 52-61https://doi.org/10.5551/jat.25593
Coenzyme A, Acyltransferase AC, Reza JZ, Doosti M, Salehipour M, Packnejad M, Mojarrad M, Heidari M, Emamian ES. Modulation peroxisome proliferators activated receptor alpha (ACAT1) gene expression by fatty acids in foam cell. 2009;7:1-7. doi:10.1186/1476-511X-8-38
- Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation.Prostaglandins Leukot Essent Fat Acids. 2021; 164102219https://doi.org/10.1016/j.plefa.2020.102219
- Concomitant use of rosuvastatin and eicosapentaenoic acid significantly prevents native coronary atherosclerotic progression in patients with in-stent neoatherosclerosis.Circ J. 2020; 84: 1826-1836https://doi.org/10.1253/circj.CJ-20-0199
- Orally administered eicosapentaenoic acid reduces and stabilizes atherosclerotic lesions in ApoE-deficient mice.Atherosclerosis. 2008; 197: 524-533https://doi.org/10.1016/j.atherosclerosis.2007.07.023
- Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice.J Clin Invest. 2008; 118: 3012-3024https://doi.org/10.1172/JCI32750
- Effects of intracellular free cholesterol accumulation on macrophage viability: A model for foam cell death.Arterioscler Thromb Vasc Biol. 1998; 18: 423-431https://doi.org/10.1161/01.ATV.18.3.423
- Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study.Lancet. 2021; 397: 985-995https://doi.org/10.1016/S0140-6736(21)00249-X
- Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.Lancet. 2007; 369: 1090-1098https://doi.org/10.1016/S0140-6736(07)60527-3
- Ballantyne CM. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.N Engl J Med. 2019; 380: 11-22https://doi.org/10.1056/nejmoa1812792
Article info
Publication history
Published online: December 02, 2022
Accepted:
November 24,
2022
Received:
July 6,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 National Lipid Association. Published by Elsevier Inc. All rights reserved.
