Infusion of Reconstituted HDL leads to Acute Changes in Human Atherosclerotic Plaque In Vivo

Abstract

Background:High-density lipoprotein (HDL) is an inverse predictor of cardiovascular events. Recent studies have showna reduction inplaque volumeand change inplaque ultrasound characteristics after four infusions of reconstitutedHDL.Whether rHDL infusion leads to acute changes in plaque composition in humans is not known. Methods and results:Patientswith symptom limiting claudication planned for percutaneous superficial femoral artery (sfa) revascularisation were randomised to either placebo or IV r HDL infusion (80mg/kg given over 4 h). 5–7 days following the infusion patients returned and revascularisation was performed including atherectomy (Foxhollow CA) to excise plaque from the sfa. 18 patients (15 male) average age 69± 10 years (mean±S.D.) were recruited. 10 had a history of documented coronary artery disease and all patients were on aspirin and 16 on statins. 9 of the patients received r HDL and 9 placebo. In the SFA plaque there was significantly less Vascular Cell Adhesion Molecule staining (23± 9 vs. 41.8± 3, p< 0.05) evidence of eral arterial tonometry (RH-PAT) measures digital pulse volume changes during reactive hyperaemia and is an alternative assessment of endothelial function. Central pulse wave velocity (PWV) is considered the best estimate of aortic stiffness. Method: Pressure waveforms were acquired in 20 healthy males (24± 5 years) from the carotid and femoral artery and PWV calculated as the quotient of foot-to-foot pressure wave delay and distance. Salbutamol (an endothelial dependant agent) was given 25min after GTN (an endothelial independent agent) was administered. Salbutamol:GTN index is the ratio of change in augmentation index (AIx)with salbutamol relative to thatwithGTN.Peak RH-PAT ratio is the ratio of the peak digital pulse volume during reactive hyperemia divided by that at baseline. Results: Peak RH-PAT ratio was inversely associated with systolic, diastolic and mean blood pressures (all p< 0.05, r2 = 0.25, r2 = 0.26, r2 = 0.23, respectively). Radial salbutamol:GTN indexwas related to peakRH-PAT ratio (p< 0.05, r2 = 0.245) and PWV (p< 0.001, r2 = 0.52). Carotid salbutamol:GTN index was not associated with the peak RH-PAT ratio or with PWV. Conclusion: In contrast to the radial pressure waveform, changes in carotid AIx do not reflect indices of endothelial function. Thismaybe explainedby the influence of arterial stiffness during pressure propagation.