Possible plaque buster offers new hope

HDL could become a treatment for heart disease.

(This article was first printed in the March 2004 issue of the Harvard Heart Letter. For more information or to order, please go to http://www.health.harvard.edu/heart.)

Every year or so, news writers get to knock themselves out on a cure-for-heart-disease story. One such story touted a lab-made form of “turbocharged HDL” (good cholesterol) that acts like “liquid Drano” to “wipe out years of damaging plaque.”

Too good to be true? It is if you’re looking for a way to battle heart disease right now. A few years down the road, though, this work could throw open the door to new and effective ways to treat or prevent cardiovascular problems.

Super HDL

The story started in the late 1970s in the isolated village of Limone sul Garda in the Italian Alps. Doctors discovered that a few of the residents had very low blood levels of HDL. Without much HDL — which removes cholesterol from the bloodstream — these people should have been particularly prone to heart attacks and strokes. They weren’t. It turned out that their HDL contained Apo A-I Milano, a unique protein that made it more effective at scavenging cholesterol.

Fast forward to now. Using genetic engineering, a Michigan company made a synthetic version of Apo A-I Milano. At medical centers across the United States, almost 60 volunteers who needed an angiogram after a heart attack or bout of serious chest pain agreed to get five weekly infusions of synthetic Apo A-I Milano or a placebo. Using a miniature ultrasound camera, doctors took before-and-after pictures of a single clogged artery in each volunteer.

In those who got inactive infusions, the amount of cholesterol-filled plaque coating the inside of the artery wall grew ever so slightly over the five-week study. But among those who got the synthetic HDL protein, plaque shrank by 4%.

What’s the buzz?

There are good reasons this study had even jaded cardiologists buzzing with surprise and excitement. One is the size of the effect. Four percent doesn’t sound like much. But it’s more than has been seen with any other therapy. The other is that the synthetic HDL did this in weeks, not years.

Exciting results, to be sure. But don’t look for new treatments based on this work right away. In addition to confirming this work with Apo A-I Milano, other questions must be answered.

First, keep in mind that the synthetic HDL shrank plaque, but didn’t eliminate it. This shows it’s possible to attack plaque but doesn’t prove that doing so will get rid of it.

Second, HDL is just one part of the complex chain involved in removing cholesterol from blood vessels. It will be important to see how speeding up the “garbage collector” affects the other parts.

Third, the Apo A-I Milano study was too small and too short to offer even hints about how this treatment might affect cardiovascular disease. Researchers need to find out whether using HDL to shrink plaque translates into fewer heart attacks and strokes over the long term.

Fourth, it’s entirely possible that the HDL most of us make is every bit as effective as Apo A-I Milano at sponging cholesterol from blood vessels and ferrying it to the liver for disposal. If that turns out to be true, then a better approach might be figuring out ways to boost our own HDL instead of taking a synthetic version.

What the research will ultimately show is anyone’s guess. But one thing is certain — this discovery is rekindling interest in HDL as a target for treatment that could someday change the course of heart disease.