2003/2004 Biomarkers, Cardiovascular System, Human Lupus Biology
“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).
“We are so grateful to the lupus support groups. Without them, this idea would not have seen the light of day.” – Dr. Hahn
Subsequent LRI-funded research showed that a blood test for the dangerous form of good-cholesterol HDL can identify lupus patients with increased risk of atherosclerosis. A new study published in 2013 by Drs. Hahn and McMahon showed that the risk of atherosclerosis in women with lupus can be better predicted using a combination of lab blood tests for novel biological markers (biomarkers). The combined biomarkers were more accurate than traditional blood tests for heart disease and could be used in the future to determine which lupus patients should receive treatments to prevent heart attacks and stroke. (Arthritis & Rheumatism, September 2013)
Over 200 lupus patients in the Los Angeles area had the combination test followed by an artery ultra-sound two and a half years later, to see if atherosclerosis developed or progressed. Results showed the combination test to be more accurate and sensitive than any individual test in predicting who would develop new or more extensive plaques.
Future studies in other patient populations are needed to confirm the effectiveness of the test to predict atherosclerosis and also heart attack and stroke.
Dr. Hahn noted, “Currently we do not know what treatments can prevent atherosclerosis and life-threatening cardiovascular events in lupus patients. Identifying patients at high risk for atherosclerosis will help design clinical trials to test ways to prevent the disease.”
The research is published in the top-ranking rheumatology journal, Arthritis & Rheumatism
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.
A panel of biomarkers is associated with increased risk for the presence and progression of atherosclerosis in women with Systemic Lupus Erythematosus. McMahon M, Skaggs BJ, Grossman J, Sahakian L, Fitzgerald J, Wong WK, Lourenco E, Ragavendra N, Charles-Schoeman C, Gorn A, Karpouzas G, Taylor M, Watson K, Weisman M, Wallace DJ, Hahn BH. Arthritis Rheum. 2013 Sep 24.
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.
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.
See more here.
Rev. July 2010