Abstract 678: Administration of Intravenous High Density Lipoprotein Leads to Acute Changes in Human Atherosclerotic Plaque In Vivo

Abstract

Introduction High density lipoprotein (HDL) is an inverse predictor of cardiovascular events. Recent studies have shown a reduction in plaque volume and change in plaque ultrasound characteristics after 4 infusions of reconstituted HDL (r HDL CSL-111) given weekly over 1 month. Whether rHDL infusion leads to acute changes in plaque composition in vivo is not known. Methods Patients with symptom limiting claudication planned for percutaneous superficial femoral artery (sfa) revascularisation were randomised in a double blind manner to either placebo or IV r HDL (80mg/Kg given over 4 hrs). Prior to the treatment bloods were taken for measurement of lipid levels and inflammatory markers. 5–7 days following the infusion patients returned, repeat bloods were taken for lipids and inflammatory markers and revascularisation was performed including atherectomy (Foxhollow CA) to excise plaque from the sfa. Results 10 patients (9 male) average age 65 ± 10 yrs (mean ± sd) were recruited. 7 had a history of documented coronary artery disease and all patients were on aspirin and 8 on statins. 6 of the patients received r HDL and 4 placebo. There was a significant increase in Ankle brachial index in both groups after atherectomy (0.57 ± 0.22 to 0.92 ± 0.12 (p < 0.01) in HDL gp, 0.58 ± 0.1 to 0.93 ± 0.05 (p < 0.01) in placebo gp.) There were no significant differences in LDL, HDL or CRP after the infusion in either group. In the SFA plaque there was significantly less Vascular Cell Adhesion Molecule 1(VCAM1) staining (23 ± 8.7% vs 41.8 ± 2.7% p < 0.05) and evidence of oxygen free radicals (31.5 ± 12.0 vs 90.3 ± 24.3 p < 0.05 (arbitrary units)) in the HDL treated subjects compared to placebo. The amount of lipid in the plaque tended to be lower in the HDL group. Conclusion Intravenous infusion of 1 dose of reconstituted HDL leads to acute changes in plaque with a reduction in measures of inflammation and oxidised free radicals in subjects with peripheral vascular disease. These changes may explain the presumed cardioprotective effects of HDL.