Researchers at The Cleveland Clinic have discovered that not all HDL, or "good" cholesterol, helps to protect arteries from becoming clogged with fatty deposits. Clinic researchers discovered a chemical signature for "dysfunctional" HDL, or HDL that does not protect against atherosclerosis in some individuals.
"This study helps explain why not all persons with high HDL levels are protected from getting heart disease," said Stanley Hazen, M.D., Ph.D., head of the Section of Preventive Cardiology and Rehabilitation at The Cleveland Clinic.
HDL becomes dysfunctional, Dr. Hazen said, when myeloperoxidase (MPO), an enzyme present in white blood cells, inhibits the HDL's ability to keep LDL, or "bad" cholesterol, from building up in artery walls.
Previous Cleveland Clinic research led by Dr. Hazen found that in patients seeking emergency care for chest pain, elevated MPO levels identified who was at risk for heart attack, bypass surgery or death within the next six months. A new test is being developed at the Clinic to measure MPO levels and determine heart-disease risk.
The present study shows for the first time a link among MPO, HDL and HDL's role in removing bad cholesterol from arteries. The study also describes the mechanism of how dysfunctional HDL is made.
Results of the study indicate that apolipoprotein A-I, or apoA-I, the primary protein found in HDL, is targeted for damage by MPO, disrupting HDL function. The new study suggests that MPO and apoA-I interactions play a significant role in a person's overall risk for cardiac disease.
A specific "chemical fingerprint" for MPO-damaged HDL was discovered in the blood of people with heart disease. Those with a high level of this marker showed a 16-fold increase in heart-disease risk. Thus, the study suggests this new test for dysfunctional HDL could be a 10-fold better predictor of heart- disease risk compared to cholesterol levels alone.