Bevra Hahn, MD

University of California at Los Angeles, CA

2003/2004 Cardiovascular System
2003/2004 Biomarkers

“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 lupus patients,” explained Dr. Hahn.

But with LRI funding, Dr. Hahn and colleague Maureen McMahon, MD, have made a major breakthrough on heart disease in lupus, establishing that people with lupus who have elevated levels of a subtype of normally “good” high density lipoprotein-pro-inflammatory HDL, or piHDL-run a 10-fold higher risk of developing atherosclerosis.

This subtype of HDL appears to play a destructive role in people with lupus as well as rheumatoid arthritis, promoting atherosclerosis (hardening of the arteries) and heart disease in many of these individuals. PiHDL appears to provide a more reliable marker for cardiovascular risk in people with lupus than traditional risk factors alone.

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

In subsequent research involving 300 people with lupus and 168 healthy women, the presence of piHDL in those with lupus was found to confer a risk of carotid artery plaque of 17, Dr. Hahn found. She found that the presence of piHDL is also significantly associated with plaque in healthy women—but these women are far less likely than women with lupus to have piHDL (less than 10 percent do).

Strategies on the horizon

One day soon, doctors may be able to test people with lupus for this menacing form of HDL and be able to take measures to aggressively prevent or reverse the damage it can do.

Already, studies have shown that piHDL will respond to treatment with a class of cholesterol-lowering drugs known as HMG-CoA reductase inhibitors, a.k.a. statins. They might also respond to treatment with anti-oxidants. The ultimate hope and promise of this work is to identify people at risk for heart disease early and stave off end-organ damage.

“Since not everybody with lupus develops accelerated atherosclerosis, it is crucial to identify people who need treatments who can then be started on preventive treatment like statins,” Dr. Hahn explained.

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.

Select publications:

Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. McMahon M, Grossman J, FitzGerald J, Dahlin-Lee E, Wallace DJ, Thong BY, Badsha H, Kalunian K, Charles C, Navab M, Fogelman AM, Hahn BH. Arthritis Rheum. 2006 Aug;54(8):2541-9.

Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus. McMahon M, Grossman J, Skaggs B, Fitzgerald J, Sahakian L, Ragavendra N, Charles-Schoeman C, Watson K, Wong WK, Volkmann E, Chen W, Gorn A, Karpouzas G, Weisman M, Wallace DJ, Hahn BH. Arthritis Rheum. 2009 Aug;60(8):2428-37.

Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus. Volkmann ER, Grossman JM, Sahakian LJ, Skaggs BJ, FitzGerald J, Ragavendra N, Charles-Schoeman C, Chen W, Gorn A, Karpouzas G, Weisman M, Wallace DJ, Hahn BH, McMahon M. Arthritis Care Res (Hoboken). 2010 Feb;62(2):258-65.

Ongoing funding:

Dr. Hahn won a two-year, $500,000 grant—as well as an additional 2-year renewal worth $500,000— from the Alliance for Lupus Research (ALR) to pursue a “future risk” study. Based on the LRI work, colleague Dr. McMahon secured an NIH grant of $625,000 and an Arthritis Foundation Investigator award of $90,000.

Rev. July 2010

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