Small apolipoprotein(a) isoforms may predict primary patency following peripheral arterial revascularization.

BACKGROUND: High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size and inflammatory markers with lower extremity revascularization outcomes.

METHODS: 25 subjects with chronic peripheral arterial disease (PAD), underwent open or endovascular lower extremity revascularization (mean age of 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, ankle brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) 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 Lp(a) levels, and wIS with procedural outcomes: symptoms (better/worse), primary patency at 2-4 weeks, ABIs, and re-intervention within 3-6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet and anticoagulation use.

RESULTS: Median plasma Lp(a) level was 108 (44, 301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and w IS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)]. The relationship of smaller apo(a) wIS with re-intervention was not as strong [OR=1.57 (95% CI 0.96 - 2.56), p=0.07]. We observed no association between wIS with patient reported symptoms or change in ABIs.

CONCLUSIONS: In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the perioperative period and/or require re-intervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes.

KEY FINDINGS: 25 subjects with symptomatic PAD underwent open or endovascular lower extremity revascularization in a small cohort. Smaller apo(a) isoforms were associated with occlusion of the treated lesion(s) within 2-4 weeks [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)], suggesting apo(a) isoform size as a predictor of primary patency in the early period after lower extremity intervention.

TAKE HOME MESSAGE: Subjects with high Lp(a) levels, generally have smaller apo(a) isoform sizes. We find that, in this small cohort, patients undergoing peripheral arterial revascularization subjects with small isoforms are at an increased risk of treated vessel occlusion in the perioperative period.

TABLE OF CONTENTS SUMMARY: Subjects with symptomatic PAD requiring lower extremity revascularization have high median Lp(a) levels. Individuals with smaller apo(a) weighted isoform size (wIS) have lower primary patency rates and/or require re-intervention.