Abstract

Introduction: High Lp(a) is associated with adverse limb events in patients undergoing lower extremity (LE) revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apo(a) isoforms whose variations in size are driven by the number of kringle IV type 2 repeats. We examined the role of apo(a) size in LE revascularization outcomes. Methods: 25 subjects with symptomatic PAD, Rutherford stage 4 or less underwent open or endovascular LE revascularization (age 66.7±9.7 years; F=12, M=13; Black=8, Hispanic=5, and White=12). Pre- and post-operative medical history, self-reported symptoms, ABIs, and LE ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hsCRP, TNFa) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size ( wIS ) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between wIS and procedural outcomes: symptoms (better/worse), patency of treated lesion(s) in the postoperative period (<1 month), change in ABI, and re-intervention <6 months. We controlled for age, sex, smoking, statin and antiplatelet use. Results: Median plasma Lp(a) level was 108 (44, 301) nmol/L. The mean apoB100 level was 168.0±65.8 mg/dl. As expected, plasma Lp(a) levels were inversely correlated with wIS (R2 = 0.20; p=0.00001). Interestingly, plasma Lp(a) levels and w IS were not associated with any of the measured plasma pro-inflammatory markers. However, small apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period [OR=2.32 (95% CI 1.08 to 4.9, p= 0.03)]. The relationship of small apo(a) wIS with re-intervention was not as strong [OR=1.59 (95% CI 0.97 to 2.62), p=0.07)]. We observed no association between wIS with patient reported symptoms or change in ABI. Conclusions: Subjects with small apo(a) isoform sizes undergoing peripheral arterial revascularization may be more likely to experience occlusion in the perioperative period and/or require re-intervention. Further studies identifying the mechanism and possible relationship of these findings to detrimental long-term peripheral vascular outcomes are warranted.

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