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【medical-news】新研究：自身去脂化HDL使得冠状动
In an interview with heartwire, Waksman stressed the preliminary nature of the study but also highlighted the attractiveness of an HDL-boosting strategy derived from the patient's own blood.
Other studies have established that increasing pre-beta HDL increases cholesterol efflux and that pre-beta HDL is the most effective form of HDL for lipid removal from arterial plaque via reverse cholesterol transport. Plasma delipidation, through apheresis, converts alpha HDL to pre-beta HDL and in theory may lead to regression of atherosclerosis, something preclinical research has demonstrated in a rabbit model, Waksman explained. He likened pre-beta HDL to an "empty dump truck" with space to transport cholesterol out of arterial plaques, as opposed to the more prevalent alpha HDL, which functions more like a "full dump trunk." The delipidation process converts alpha HDL to pre-beta HDL.
Study Conducted in ACS Patients
Waksman et al's study randomized 28 patients with ACS scheduled for cardiac catheterization to either HDL delipidation and reinfusion or undelipidated plasma reinfusion. The HDL apheresis/reinfusion procedure was repeated seven times, once per week, and IVUS was performed two weeks after the final procedure. According to Waksman, the weekly lipid apheresis/reinfusion schedule was borrowed from the high-profile ApoA-1 Milano (ETC-216, Pfizer) study, which showed improvements on atherosclerotic burden following an infusion regimen of a recombinant HDL mimetic [1].
For the first part of the study, investigators confirmed that the apheresis procedure did indeed increase the proportion of pre-beta HDL (from about 5.6% in the sample to 92.8% in the sample) and reduced the proportion of alpha HDL (from about 92.8% of the sample to 20.9% in the sample). Associated with the increase in pre-beta HDL was a fivefold rise in cholesterol efflux seen in patients receiving the delipidated plasma vs the control group, they report. All reinfusion sessions were well tolerated, and there was no signal of an adverse biochemical or hemodynamic reaction to therapy.
Possible Effects on Atherosclerosis?
In exploratory IVUS analyses, reductions in total atheroma volume and in plaque burden were greater in the delipidation group, as compared with the control group, although the differences from baseline were not statistically significant--likely due to the small study size. In an interview with heartwire, Waksman called the observations "provocative," particularly since the changes were occurring over such a short period of time.
By way of comparison, he and his colleagues compared their IVUS findings with those of Nissen et al's study of recombinant apoA-1 Milano and found that the effects on atheroma volume were comparable between the two studies.
Study Comparison IVUS changes Delipidation (n=14) Control (n=14) IVUS results from ApoA-1 Milano study (n=36)*
Change in total atheroma volume (mm3) -12.18 2.80 -14.1
Change in plaque burden (%) -1.0 0.0 -1.1
Change in 10-mm most diseased subsegment--atheroma volume (mm3) -6.24 -1.73 -7.20
*Nissen S et al. JAMA 2003; 290:2292-2300
While a larger trial is necessary to confirm the results as well as determine the optimum number of repeats necessary for therapy, Waksman is cautiously optimistic about the findings. To heartwire, he explained that the aim of the therapy would be plaque stabilization, so that a patient, theoretically, would require the procedure only to "stabilize" their ACS.
But he points out that most of the patients in this study were already taking statins, so the changes seen in the plaques were on top of statin therapy. So far, he said, the strategy seems safe and would be a welcome addition in a field that has seen major disappointment in recent years. "The HDL story is not over," he said, "but there are not a lot of options left."
Discussing the study results after their presentation, Dr Peter Fitzgerald (Stanford School of Medicine, CA), whose core lab was one of two that conducted the blinded analysis of the IVUS data, suggested that the results were intriguing but that, given the sample size, would have to be "taken with a grain of salt."
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作者:admin@医学,生命科学 2010-10-23 17:11
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