Key result
A higher EPA/AA ratio was independently associated with a lower risk of MACE only in patients with a higher EPA/AA lipid phenotype (HR 0.63; 95% CI 0.47-0.83; P=.001).
Why the study?
Residual cardiovascular risk persists in stable coronary artery disease despite improved LDL-C control.
Does the EPA/AA ratio predict MACE differently based on multidimensional lipid phenotypes in patients undergoing elective PCI or coronary angiography?
Cohort
Does the EPA/AA ratio predict MACE differently based on multidimensional lipid phenotypes in patients undergoing elective PCI or coronary angiography?
Multidimensional lipid phenotyping, specifically the EPA/AA ratio, may help stratify residual cardiovascular risk in patients undergoing elective PCI or angiography.
Answers are grounded in this paper and cite their sources.
EPA/AA ratio may stratify residual MACE risk within lipid clusters post-elective PCI; hypothesis-generating and should not yet change practice.
BACKGROUND: Residual cardiovascular risk persists in stable coronary artery disease despite improved low-density lipoprotein cholesterol (LDL-C) control. OBJECTIVE: We aimed to identify lipid phenotypes using multidimensional lipid profiling and to evaluate phenotype-dependent associations of fatty acid balance and lipoprotein(a) [Lp(a)] with major adverse cardiovascular events (MACE). METHODS: This retrospective study included patients undergoing elective percutaneous coronary intervention or coronary angiography. The day after the procedure, LDL-C, triglycerides (TG), remnant-like particle cholesterol (RLP-C), fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], arachidonic acid [AA], dihomo-γ-linolenic acid [DGLA]), malondialdehyde-modified low-density lipoprotein (MDA-LDL), and Lp(a) were measured; clustering using lipid parameters, including EPA/AA, DHA/AA, and DGLA/AA, identified lipid phenotypes. The primary endpoint was MACE (cardiovascular death, myocardial infarction, or stroke); the secondary endpoint was ischemia-driven repeat revascularization. RESULTS: Two phenotypes were identified: Cluster 1 (TG/RLP-C/MDA-LDL dominant phenotype) and Cluster 2 (higher EPA/AA lipid phenotype). During a median follow-up of 1356 days, a total of 86 MACE events occurred. Events were more frequent in Cluster 2 in unadjusted analysis (log-rank P = .036), but the association was attenuated after adjustment. Repeat revascularization did not differ between phenotypes. A higher EPA/AA ratio was independently associated with lower MACE risk only in Cluster 2 (HR 0.63, 95% CI 0.47-0.83; P = .001), with a significant interaction (likelihood ratio P = .012). Lp(a) showed a phenotype-specific, time-dependent association with early MACE only in Cluster 2. CONCLUSION: Fatty acid balance may have phenotype-dependent prognostic relevance. These findings support further investigation of multidimensional lipid phenotyping in residual cardiovascular risk assessment, although they should be interpreted as exploratory.
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Inoue et al. (2026) conducted a cohort in Stable coronary artery disease. Higher EPA/AA ratio vs. Lower EPA/AA ratio was evaluated on MACE (cardiovascular death, myocardial infarction, or stroke) (HR 0.63, 95% CI 0.47-0.83, p=.001). A higher EPA/AA ratio was independently associated with a lower risk of MACE only in patients with a higher EPA/AA lipid phenotype (HR 0.63; 95% CI 0.47-0.83; P=.001).
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