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Cardiovascular Disease And Lupus

ACR Special Report: Philadelphia, PA, October 18-21, 2009

Cardiovascular Disease in Lupus

People with lupus have a significantly increased risk of premature coronary heart disease (CHD) or atherosclerosis, stroke and other cardiovascular-related conditions than those without lupus. Some studies suggest risks of people with lupus are more than 50 times that of the general population.xii That is why it is so important to understand what underlies early atherosclerosis in women with lupus so researchers can develop ways to prevent and treat the condition.

This focus was evident at this year's ACR conference, with numerous posters and oral presentations focused on cardiovascular disease in people with lupus. Among the presentations:

Genetic link between lupus and stroke: ALR-funded researcher Lindsay Criswell, MD, of the University of California, San Francisco and her colleagues presented the results of two studies demonstrating that genes thought to be associated with stroke and other clotting abnormalities (thrombosis) in people with lupus were also associated with the development of the disease itself.xiii

One study, the largest and most ethnically diverse analysis to date to evaluate novel genetic risk factors for thrombosis in people with lupus, strongly suggests that certain inherited changes in genes — along with other known risk factors, such as the presence of antiphospholipid antibodies — help explain part of the increased risk of thrombosis in SLE patients.xiv

What this means for people with lupus? As researchers work to uncover the risk factors for developing blood clots in patients with lupus, genetic analyses could help them better predict which patients are at highest risk for this serious complication.

HDL and atherosclerosis in lupus: We are used to thinking of HDL cholesterol as the "good" cholesterol, the garbage truck of the blood vessels whose job it is to cart away the "bad" atherosclerotic LDL cholesterol to the liver for disposal and protect it from oxidation, the process that enables it to burrow into artery walls and begin the atherosclerotic process.

However, thanks to work by ALR-funded researchers and others, we now know that abnormal, pro-inflammatory HDL (piHDL) can exist in people with lupus and other autoimmune diseases, likely contributing to atherosclerosis.

In one study presented by Maureen A. McMahon, MD, of the University of California-Los Angeles, which also involved ALR grantees Bevra Hahn, MD, also of UCLA, and Michelle Petri, MD, of Johns Hopkins University, the researchers followed women with lupus who did not have cardiovascular disease and compared their plaque levels and piHDL presence to those of women without lupus. The goal was to see if piHDL cholesterol existed before the plaque or was related to the plaque itself.

Overall, researchers found that:

  • Women who had piHDL at the beginning of the study had a 24-fold increased risk of developing plaque or having existing plaque get worse compared to women with normal HDL.
  • Older age, diabetes, and initial presence of plaque also increased the risk of progressing plaque, but to a much lower degree than piHDL.
  • The presence of piHDL remained stable over time, suggesting that it was not triggered by the plaque, but existed before plaque development.xv

What this means for people with lupus? The presence of piHDL may serve as a marker to identify women with lupus who have the highest risk of cardiovascular disease so more intense preventive steps can be initiated.

Exercise and Pro-Inflammatory HDL

Women with lupus who rarely exercised were more likely to have pro-inflammatory HDL and atherosclerosis than women who were more active, regardless of disease severity. "The key to reducing that risk," said lead author Elizabeth Volkmann, MD, of UCLA, "is strenuous activity that increases heart rate for at least 30 minutes a day, according to the study."xvi

Peeking at Blood Vessel Walls: ALR-grantee Paolo C. Colombo, MD, of Columbia University College of Physicians and Surgeons, described a new, minimally invasive, safe method to sample and study the endothelium, the inner layer of blood vessels that plays a key role in atherosclerosis. The new method Dr. Colombo and his colleagues describe can help researchers find lupus-specific processes that begin, sustain and possibly, end inflammation and atherosclerosis in people with lupus.xvii

What it means for people with lupus? The information learned by studying the endothelium could lead to new methods of preventing and treating early atherosclerosis in people with lupus.


References

xii Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am J Epidemiol, 1997;145:408–15

xiii Kaiser R, Li Y, Chang M, et al. Novel SNPs Associated with Systemic Lupus Erythematosus (SLE). Poster presented at the 73rd Annual Scientific Meeting of the American College of Rheumatology, October 18, 2009; Philadelphia, PA.

xiv Kaiser, R. Li, Y. Chang, M. Catanese, J. Begovich, AB. Criswell, LA. Genetic Risk Factors for Thrombosis in An Ethnically Diverse Systemic Lupus Erythematosus (SLE) Population. Poster presented at the 73th Annual Scientific Meeting of the American College of Rheumatology, October 18, 2009; Philadelphia, PA.

xv Kiani A, McMahon, MM, Sahakian LJ, et al. Pro-Inflammatory High Density Lipoprotein (PiHDL) in Systemic Lupus Erythematosus. Presented at the 73th Annual Scientific Meeting of the American College of Rheumatology, October 20, 2009; Philadelphia, PA.

xvi Kiani A, McMahon, MM, Sahakian LJ, et al. Pro-Inflammatory High Density Lipoprotein (PiHDL) in Systemic Lupus Erythematosus. Presented at the 73th Annual Scientific Meeting of the American College of Rheumatology, October 20, 2009; Philadelphia, PA.

xvii Goldenberg D, Olferiev M, Onat D, et al. Expression Profiling of the Vascular Endothelium in Patients With SLE Using a Novel Methodology: Human Endothelial Sampling Coupled With Microarray Analysis. Presented at 73th Annual Scientific Meeting of the American College of Rheumatology, October 17-21, 2009; Philadelphia, PA.

 

More information about lupus and treatment advances can be found by visiting www.lupusresearch.org.

The 2009 American College of Rheumatology Meeting Special Report was made possible in part by generous support from Biogen Idec, Genentech and Johnson & Johnson.

Genentech Biogen IdecJohnson & Johnson

©2009 Alliance for Lupus Research. All Rights Reserved.

Contents herein may not be reproduced, republished or distributed without the prior written permission of the Alliance for Lupus Research. To request permission to reproduce, republish or distribute any part of this report, contact us at 212-218-2840 or email info@lupusresearch.org.


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