Study uncovers potential biomarker for lupus atherosclerosis

Candidate is a subtype of HDL cholesterol that promotes inflammation

Groundbreaking research reported at the annual meeting of the American College of Rheumatology indicates that a certain form of the normally “good” high density lipoprotein (HDL) cholesterol linked to cardiovascular health plays a counterproductive role in people with systemic lupus erythematosus (SLE) and rheumatoid arthritis, promoting atherosclerosis (hardening of the arteries) and heart disease in many of these individuals.

The menacing HDL form is pro-inflammatory HDL (piHDL), according to research by Bevra H. Hahn, MD, Maureen McMahon, MD, and colleagues at the David Geffen School of Medicine at UCLA, and it can easily be measured and, most importantly, treated. Dr. Hahn is chief of the division of rheumatology, and Dr. McMahon is an assistant clinical professor of rheumatology.

“Traditional risk factors for atherosclerosis–including high blood pressure, increased cholesterol levels, diabetes mellitus, older age and postmenopausal status–have proved ineffective for predicting atherosclerosis in SLE patients,” said Dr. Hahn, whose research is funded by the Lupus Research Institute (LRI). “Uncovering a potentially important role for pro-inflammatory HDL in the development of atherosclerotic disease in patients with SLE is an important first step toward developing strategies to prevent cardiovascular morbidity and mortality in these patients.”

Dr. Hahn notes that “pro-inflammatory HDL, which is easily measured, may provide just the sign, known as a biomarker, to determine which patients are at increased risk. If this research is successful, in two years or sooner a test may be available to screen for piHD.

According to Dr. Hahn, women with lupus are about 7 to 10 times more likely than women without the disease to suffer a heart attack or stroke–just a few of the myriad serious health problems confronting the estimated 1.5 million Americans with this chronic autoimmune disease. In lupus, the body attacks its own healthy tissues and organs in a repetitive cycle of flare-ups and remissions.

Results Reported

In the study, Dr. Hahn measured the presence of pro-inflammatory and HDL in samples of blood plasma from 154 women with SLE, 73 age matched controls, and 50 women with rheumatoid arthritis. Compared to the control group, the HDL from those with SLE contained significantly more piHDL. “We found that almost 50 percent of SLE patients, versus approximately 4 percent of controls and 20 percent of rheumatoid arthritis patients, had piHDL,” said Dr. Hahn.

In addition, piHDL was found in 8 of the 10 individuals with SLE determined to have actual atherosclerosis. The biomarker was similarly high in half of the 12 subjects with SLE that had suffered a stroke (cerebrovascular event).

“We can clearly see from these results that HDL function fails to protect against cardiovascular disease in many SLE and rheumatoid arthritis patients,” Dr. Hahn concluded. “This discovery may lead to an effective test [a fluorescence assay] to identify those at increased risk for blockage of the coronary arteries so that we can start them on preventive treatments like cholesterol-lowering statins.”