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Longitudinal Lipidomic Profile of Subclinical Peripheral Artery Disease in American Indians: The Strong Heart Family Study
ORIGINAL RESEARCH — Volume 22 — December 24, 2024
PEER REVIEWED
This figure shows that 46 lipids were significantly associated with changes in ABI. Specifically, higher levels of 37 lipids were positively associated with ABI changes, while 9 lipids, including cholesterol, were inversely associated. Notably, 3 lipids (TAG(48:2), TAG(55:1), and PI(16:0/20:4)) reduced CHD risk, while cholesterol increased it over 18 years.
Figure 1.
Baseline plasma lipid species associated with change in ABI (Q< .05). Lipids significantly associated with incident CHD are highlighted in blue. “A” or “B” in name of lipids indicates isomers. Abbreviations: ABI, ankle-brachial index; CHD, coronary heart disease; DAG, diacylglycerol; eGFR, estimate glomerular filtration rate; HR, hazard ratio; FA, fatty acid; FAHFA, fatty acid ester of hydroxy fatty acid; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; SM, sphingomyelin; TAG, triacylglycerol.
This line graph shows the improvement in predicting PAD risk when plasma lipids associated with changes in ABI are added to traditional risk factors in the prediction model. Data from 2 study centers were used for model training, and data from 1 center were used for testing. Model 1 included only traditional risk factors such as age, sex, and clinical factors. Model 2 included these factors plus 9 lipids significantly associated with ABI changes. The addition of lipids in Model 2 significantly improved PAD risk prediction, with a significant increase in model performance (P = .04).
Figure 2.
Incremental value of the identified plasma lipids associated with change in ABI for PAD risk prediction. Data used from 2 study centers (North and South Dakota and Arizona) as training set (n = 995, 32 cases), used for model training, and 1 center (Oklahoma) as the testing set (n = 788, 65 cases), used to test classification performance. Model 1 (blue line): traditional risk factors only, including age, sex, body mass index, smoking status, alcohol use, hypertension, diabetes, eGFR, and lipid-lowering medication use at baseline. Model 2 (red line): clinical factors plus 9 lipids significantly associated with change in ABI. Compared with Model 1, additional inclusion of plasma lipids (Model 2) significantly increased risk prediction for PAD; P value for increase in AUROC = .04. Abbreviations: ABI, ankle-brachial index; AUROC, area under the receiver operating characteristic curve; eGFR, estimated glomerular filtration rate, PAD, peripheral artery disease.
This graph shows that changes in 32 lipids were significantly associated with changes in ABI over 5 years (Q < .05). Among these, 6 lipids, including 3 PIs, AC(18:2), CE(18:3), and LPE(22:5), were positively associated with change in ABI, while LPC(p-18:0)/LPC(o-18:1) was inversely associated.
Figure 3.
Manhattan plot displaying the longitudinal associations between change in plasma lipids and change in ABI during an average of 5-years follow-up. The dashed lines represent significance level at P= .05 and Q= .05. Abbreviation: ABI, ankle-brachial index.
This graph shows altered levels of multiple lipid species, such as ACs, FAs, glycerophospholipids (ie, PCs, PEs, PIs), and TAGs, were significantly associated with ABI among American Indians. Notably, 4 lipids, including GlcCer(d14:1[4E]/20:0[2OH]), PC(36:1), TAG(55:5)/TAG(17:0/18:1/20:4), and TAG(56:5) C, were inversely associated with ABI at both time points, independent of risk factors.
Figure 4.
Top-ranked plasma lipids associated with ABI at P< .05 identified at baseline or 5-year follow-up. Lipids significantly associated with ABI (P< .05) at baseline, at follow-up, and in the meta-analysis are highlighted in blue. “A,” “B,” or “C” in name of lipids indicates isomers. Abbreviations: ABI, ankle-brachial index; AC; acylcarnitine; CE, cholesterol ester; CER, ceramide; eGFR, estimated glomerular filtration rate; FA, fatty acid; GlcCer, glycosylceramide; HR, hazard ratio; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; SM, sphingomyelin; TAG, triacylglycerol.
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