Synthetic HDL
Cleansing Coronary Arteries with Synthetic HDL
What is the problem and what is known about it so far?
Cardiovascular disease is the number one cause of death in the United States for both men and women. Often, cardiovascular disease is associated with atherosclerosis, which results from complex deposits of material (including cholesterol) in arterial vessel walls. It is known that high density lipoprotein (HDL), also known as "good cholesterol", plays an important role in removing cholesterol from the blood stream and returning it to the liver for reprocessing.
Why did the researchers do this particular study?
To find out if atherosclerotic deposits in coronary arteries (heart blood vessels) could be reduced by giving synthetic HDL to patients.
Who was studied?
47 patients between the ages of 30 and 75 years old who had been diagnosed with Acute Coronary Syndrome (ACS includes unstable angina and small heart attacks) and who had not undergone angioplasty (unblocking arteries with a balloon).
How was the study done?
Before receiving any treatment all patients participating had images of their coronary arteries taken using ultrasound techniques. Each patient was then randomly assigned to one of three groups: 1) received a solution containing no drugs; 2) received a solution containing a low dose of synthetic HDL; 3) received a solution containing a high dose of synthetic HDL. The patients received their solutions once a week for five weeks. Images were then taken again of the coronary arteries using the same ultrasound techniques. The ultrasound images from before and after treatment were compared to see if there had been any changes in atherosclerotic deposits.
What did the researchers find?
The volume (size) of atherosclerotic deposits in patients who received synthetic HDL was reduced by an average of 4.2 % after 5 weeks of treatment. The data was not analyzed to see if high dose HDL or low dose HDL worked better, however, two patients in the high dose group had to be removed from the study because of bad reactions. The volume of atherosclerotic deposits in patients who received a solution containing no drugs was not changed over the 5 weeks. Interestingly, even though the atherosclerotic volume declined in the HDL groups, the luminal diameter (size of the opening inside the blood vessel that allows blood flow) did not increase in any of the three groups.
What were the limitations of the study?
This study followed very few patients for a very small period of time. It is not known if it is safe to give someone synthetic HDL for long periods of time, or if the effectiveness of synthetic HDL would wear off with time. While reducing the volume of atherosclerotic deposits is impressive, luminal diameter of coronary arteries is probably more important in cardiovascular disease than atherosclerotic volume - and this study could not show an increase in luminal diameter. Also, the ultrasound imaging used in this study does not give a clear picture of the coronary arteries. This makes it difficult to take precise measurements and accurately compare images, which makes it difficult to feel confident that the treatment really had an important beneficial effect.
What are the implications of this study?
Synthetic HDL may reduce the size of atherosclerotic deposits over a short period of time. Further studies are needed to see if the same result can be found again and if reducing the size of the deposits can also increase coronary artery blood flow.
Summarized by Wells Chandler, College of Medicine, University of Vermont.
Summarized from "Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes: a Randomized Controlled Trial." Nissen, Steven E. et al. Journal of the American Medical Association, November 5, 2003, Volume 290, Number 17, Pages 2292-2300.
