Longitudinal Lipidomic Profile of Subclinical Peripheral Artery Disease in American Indians: The Strong Heart Family Study

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.

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.

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.

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.