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

Abstract

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

Twenty-five subjects with chronic peripheral arterial disease (PAD) underwent open or endovascular lower extremity revascularization (mean age, 66.7 ± 9.7 years; Female = 12; Male = 13; Black = 8; Hispanic = 5; and White = 12). Pre- and postoperative 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), early primary patency at 2 to 4 weeks, ABIs, and reintervention within 3 to 6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet, and anticoagulation use.

Results

Median plasma Lp(a) level was 108 (interrquartile range, 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 wIS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period (odds ratio, 1.97; 95% confidence interval, 1.01-3.86; P < .05). The relationship of smaller apo(a) wIS with reintervention was not as strong (odds ratio, 1.57; 95% confidence interval, 0.96-2.56; P = .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 postoperative period and/or require reintervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes.