Circulating lysophosphatidylethanolamine species are associated with pericoronary adipose tissue inflammation and coronary atherosclerotic burden in type 2 diabetes

Figures

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  Figure 1.. Characterization of the lipidomic signature. (A). Study workflow. Participants with T2DM and suspected or established CAD were enrolled from the GADA cohort. All participants underwent CTA, invasive CAG, and plasma lipidomic profiling. Participants were stratified according to FAI: FAI < −70.1 HU (n = 132) and FAI ≥ −70.1 HU (n = 44). (B). Violin plots showing the normalized relative abundance of identified lipid classes. (C). Violin plots showing the normalized relative abundance of fatty acids within lipid species. T2DM, type 2 diabetes mellitus; CAD, coronary artery disease; CTA, computed tomography angiography; CAG, coronary angiography; FAI, fat attenuation index.

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  Figure 2.. Lipid species consistently associated with pericoronary FAI in multivariable analyses (A). Multivariable logistic regression analysis of lipid species associated with elevated pericoronary inflammation, defined as FAI ≥ −70.1 HU. Odds ratios (ORs) and 95% confidence intervals (CIs) are shown for individual lipid species grouped by lipid class. (B). Volcano plots showing the association of individual lipid species with elevated FAI in multivariable logistic regression models. The x-axis represents the OR, and the y-axis represents −log10 (P value). Volcano plots are stratified by lipid class for visualization. (C). Multivariable linear regression analysis of lipid species associated with continuous FAI values. β coefficients and 95% CIs are shown for individual lipid species grouped by lipid class. (D). Volcano plots showing the association of individual lipid species with continuous FAI in multivariable linear regression models. The x-axis represents the β coefficient, and the y-axis represents −log10 (P value). Volcano plots are stratified by lipid class for visualization. (E). Venn diagram showing the overlap between lipid species associated with FAI in logistic and linear…

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  Figure 3.. Association of pericoronary inflammation and selected lipid species with coronary atherosclerotic burden. (A–B). Violin plots showing the distribution of Gensini score (A) and SYNTAX score (B) in participants with FAI < −70.1 HU (n = 132) and FAI ≥ −70.1 HU (n = 44). Between-group differences were assessed using the Mann–Whitney U test. (C–D). Scatter plots showing the associations of FAI with Gensini score (C; Spearman’s ρ = 0.52, P < 0.001) and SYNTAX score (D; Spearman’s ρ = 0.45, P < 0.001). (E–F). Forest plots showing the associations of selected lipid species with Gensini score (E) and SYNTAX score (F) in multivariable linear regression models. Models were adjusted for age, sex, body mass index, smoking status, hypertension history, estimated glomerular filtration rate, glycated hemoglobin A1c, non–high-density lipoprotein cholesterol, triglycerides, and log2-transformed high-sensitivity C-reactive protein. Processed lipid abundance refers to log2-transformed and ComBat-corrected normalized lipid abundance. β coefficients are presented per 1-SD increase in processed lipid abundance, with 95% confidence intervals. All P values are two-sided.

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  Figure 4.. Exploratory mediation analysis of FAI in the associations between LPE species and coronary atherosclerotic burden. (A–F). Exploratory mediation estimates for FAI in the associations of LPE (18:1), LPE (18:2), and LPE (20:4) with angiographic coronary atherosclerotic burden, assessed by Gensini and SYNTAX scores. Panels A–C show analyses for Gensini score, and panels D–F show analyses for SYNTAX score. Indirect effect, direct effect, and proportion mediated are shown with 95% confidence intervals derived from 5,000 nonparametric bootstrap resamples. All P values are two-sided. Models were adjusted for age, sex, body mass index, smoking status, hypertension history, estimated glomerular filtration rate, glycated hemoglobin A1c, non–high-density lipoprotein cholesterol, triglycerides, and log2-transformed high-sensitivity C-reactive protein. FAI, fat attenuation index; LPE, lysophosphatidylethanolamine; CI, confidence interval; PM, proportion mediated.