It's Not Just Lipoprotein Density - Particle Size is Important (2)

Summarized by Robert W. Griffith, MD
December 4, 2003

Introduction

There's a small village in northern Italy, Limone sul Garda, where there are 40 people who have a variation of a naturally occurring lipoprotein, Apo-I Milano. These individuals have very low blood levels of high-density lipoprotein (HDL) cholesterol, but they have increased longevity, and a much lower amount of atherosclerosis than would be expected based on their HDL levels.

Because atherosclerosis is reduced in these subjects with Apo-I Milano lipoprotein, investigators studied the administration of the protein to animals with experimentally-induced atherosclerosis. They used a complex of Apo-I Milano with a naturally occurring phospholipid, to mimic the properties of HDL. Studies in mice and rabbits showed a rapid reduction in atherosclerosis as soon as 48 hours after an intravenous infusion of the complex. This led to the first clinical trail in humans, which has been reported in JAMA and is summarized here.

Method

A double-blind randomized study was done in 57 patients with acute coronary syndromes. Intravenous ultrasound was used to measure the degree of atherosclerosis, using catheterization of the appropriate coronary artery. This was done before and after the experimental treatment.

Patients were given 5 weekly intravenous infusions of either a placebo, a low dose, or a high dose of the Apo-I Milano complex. The primary efficacy variable was a change in the percentage volume of atheroma after 5 weeks' therapy. Secondary variables were changes in the mean thickness of the atheroma at its widest part, and the total volume of atheroma in a given length of artery.

Results

Of the 57 patients in the study, 12 received placebo infusions, 23 received low- dose (15 mg/kg), and 22 high-dose (45 mg/kg) infusions. At the baseline ultrasound exam, the mean percentage volume of atheroma ranged from 35% to 40%, and the mean maximum thickness from 0.65 mm to 0.82 mm.

After the 5-week experimental treatment, the percentage volume of atheroma had increased a little (0.14%) in the placebo group, and was considerable decreased (-0.06%) in the low- and high-dose treatment groups (results combined). There was no evidence that the higher dose was more effective than the low dose infusion with respect to percentage atheroma volume reduction.

The mean thickness of atheroma was reduced by 0.042 mm with the Apo-I Milano complex therapy, and the mean volume of atheroma by 14 cubic mm, compared with virtually no changes in the placebo patients.

Slight nausea was reported by patients from all three treatment groups. One patient in the high-dose Apo-I Milano complex group had a reaction that was considered to be possibly due to the therapy - chills, nausea, vomiting, and a mild rash.

Comment

This was a preliminary study of an entirely new approach to the problem of coronary atherosclerosis. Although the changes demonstrated were quite small, they were statistically significant, and significant reversal of atheroma was demonstrated with only 5 weekly treatments.

Apo-I Milano differs from other apo-lipoproteins in a way that allows the formation of large HDL particles. And it's recently been shown that larger HDL particles are linked with less atherosclerosis and increased longevity - see: "It's Not Just Lipoprotein Density - Particle Size is Important (1)".

In one of the news interviews given by the investigators, someone spoke of the Apo-I Milano complex as being "like Drano for the arteries". Certainly, anything that can "clean out" atheroma in the way demonstrated in this study deserves extensive further investigation, and may become, one day, an important new treatment modality.

Source

• Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes. SE. Nissen, T. Tsunoda, EM. Tuzcu,  et al., JAMA, 2003, vol. 290, pp. 2292--2300

Related Links
It's Not Just Lipoprotein Density - Particle Size is Important (1)
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