Association between EPA/AA ratio and plaque characteristics in stable CAD patients on statins
Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease
Literature - Asakura K, Minami Y, Nagata T, et al. - J Clin Lipidol. 2023 Jan-Feb;17(1):189-196. doi: 10.1016/j.jacl.2022.11.011Introduction and methods
Background
In patients with coronary artery disease (CAD), a low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with subsequent adverse coronary events [1,2], even in those on statin treatment [3]. However, the association of the EPA/AA ratio with coronary plaque characteristics in statin-treated patients with established CAD remains to be elucidated.
Aim of the study
The authors performed a detailed assessment of the characteristics of nonculprit coronary plaques and investigated the association between these characteristics and the EPA/AA ratio in statin-treated patients with CAD.
Methods
In this single-center, retrospective, cross-sectional, observational study conducted in Japan, 370 consecutive patients with stable CAD treated with (mostly low- or moderate-intensity) statins who underwent optical coherence tomography (OCT)–guided PCI for a culprit plaque were included. Characteristics of nonculprit plaques within the same coronary artery that were incidentally imaged were analyzed. Serum levels of EPA and AA and were measured within 24 hours prior to the OCT assessment.
Main results
- Patients with a low EPA/AA ratio (<0.4; n=255) showed a higher prevalence of lipid-rich nonculprit plaques (58.8% vs. 41.7%; P=0.003) and plaques with macrophages (56.5% vs. 31.3%; P<0.001) compared with patients with a high EPA/AA ratio (≥0.4; n=115). There were no differences between the groups in the prevalence of layered plaques, microvessels, thin-cap fibroatheromas, or cholesterol crystals.
- In patients with LDL-c<100 mg/dL, the prevalences of lipid-rich plaques and plaques with macrophages were higher in patients with EPA/AA ratio <0.4 than in those with EPA/AA ratio ≥0.4.
- Patients with EPA/AA ratio <0.4 and LDL-c ≥100 mg/dL displayed a higher prevalence of lipid-rich plaques (OR: 1.896; 95%CI: 1.017–3.569; P=0.045), plaques with macrophages (OR: 3.754; 95%CI: 1.966–7.352; P<0.001), and thin-cap fibroatheromas atheromas (OR: 2.750; 95%CI: 1.182–6.988; P=0.024) compared with patients with EPA/AA ratio ≥0.4 and LDL-c <100 mg/dL.
- Multivariate analyses showed that EPA/AA ratio <0.4 was independently associated with a higher prevalence of lipid-rich plaques (OR: 1.842; 95%CI: 1.142–2.990; P=0.013), plaques with macrophages (OR: 2.953; 95%CI: 1.796–4.936; P<0.001), and cholesterol crystals (OR: 2.650; 95%CI: 1.141–7.247; P=0.036 ).
Conclusion
In this Japanese, retrospective, observational study of statin-treated patients with stable CAD, a low EPA/AA ratio (<0.4) was associated with a higher prevalence of vulnerable characteristics of nonculprit coronary plaques as assessed with OCT, such as lipid-richness and macrophage infiltration, even if LDL-c <100 mg/dL.
The authors believe that their results, taken together with the findings of earlier EPA treatment trials, “may imply the adjunctive and synergistic role of EPA, in addition to LDL-c, in the change in morphologies of coronary plaques and subsequent development of clinical events.”
References
1. Wakabayashi Y, Funayama H, Ugata Y, Taniguchi Y, Hoshino H, Ako J, Momomura S. Low eicosapentaenoic acid to arachidonic acid ratio is associated with thin-cap fibroatheroma determined by optical coherence tomography. J Cardiol. 2015;66:482–488. doi: 10.1016/j.jjcc.2015.01.008
2. Hasegawa T, Otsuka K, Iguchi T, Matsumoto K, Ehara S, Nakata S, Nishimura S, Kataoka T, Shimada K, Yoshiyama M. Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study. Heart Vessels. 2014;29:596–602. doi: 10.1007/s00380-013-0404-4
3. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease - Secondary prevention analysis from JELIS. Circ J. 2009;73:1283–1290. doi: 10.1253/circj.CJ-08-1197
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