Interferon-associated risk for premature heart disease among people with lupus
What is the topic?
Lupus is associated with high rates of premature heart disease. Among people with lupus, traditional risk factors for heart disease are less important than lupus disease activity. Type I interferon, which plays a major role in lupus, may also contribute significantly to premature heart disease among people with lupus. A greater understanding of the relationship between interferon and premature heart disease among people with lupus can be useful in guiding their treatment and care.
What did the researchers hope to learn?
The researchers hoped to learn about the relationship between type I interferon and premature heart disease risk among people with lupus.
Who was studied?
Lupus patients (n=95) were recruited to the study from the Michigan Lupus Cohort if they were less than 55 years old and had no previous history of heart disease. Participants were excluded from the study if they were smokers (currently or within the previous six months), had diabetes, were pregnant, had a current infection, or were taking two or more kinds of specific classes of drugs to control high blood pressure.
For purposes of comparison, non-lupus participants (n=38) meeting the same eligibility criteria were recruited to the study from the University of Michigan Women’s Health Registry. These participants were matched by age and sex to the lupus patients.
How was the study conducted?
Lupus disease activity was measured by use of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and organ damage was assessed by use of the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index.
The researchers examined the relationship between type I interferon and three measures of premature heart disease: flow-mediated dilation, carotid intima media thickness, and coronary calcification. Flow-mediated dilation (a measurement of dysfunction of endothelial cells, located in the inner lining of blood vessels) and carotid intima media thickness (a measurement of the thickness of the carotid artery wall) were measured by ultrasound. Coronary calcification (a measurement of the amount of calcium bound to the walls of the coronary artery) was measured by computerized tomography. Also, several lupus biomarkers were measured in the blood. In addition, blood serum from both lupus patients and non-lupus participants were tested for the ability to cause increases in genetic activity induced by interferon in cells studied in a dish (a measurement of “interferon activity”).
What did the researchers find?
Lupus patients and non-lupus participants were similar in terms of age, race, traditional heart disease risk factors, body mass index, blood pressure, total cholesterol, triglycerides (fat in the blood), and family history of heart disease. The lupus patients were taking a variety of medications, including: ant-malarials (62%), prednisone (61%), non-steroidal anti-inflammatory drugs (NSAIDS) and/or aspirin (46%), mycophenolate mofetil (22%), azathioprine (11%), methotrexate (8%), statins or cholesterol-lowering drugs (8%), and cyclophosphamide (4%). Upon entry to the study, lupus patients had decreased flow-mediated dilation (indicating decreased endothelial function) as compared to non-lupus participants, but there were no significant differences in carotid intima media thickness or coronary calcification. In addition, upon entry to the study, there were no differences in interferon activity between lupus patients and non-lupus participants.
After controlling for traditional risk factors, increased interferon activity in the blood was significantly associated with decreased flow-mediated dilation (indicating endothelial cell dysfunction) in both lupus patients and non-lupus participants, increased carotid intima media thickness (indicating possible premature heart disease), as well as and severity of coronary calcification, among lupus patients.
What were the limitations of the study?
Most of the lupus patients were white females with low disease activity and relatively mild lupus manifestations. Additional studies with more male lupus patients who have greater disease activity and more severe lupus manifestations may be necessary to determine whether the current findings are applicable to other populations.
What do the results mean for you?
Type I interferon is associated with an increased risk of premature heart disease among people with lupus even in the absence of traditional risk factors for heart disease. Therefore, people with lupus may need to work with their physicians to closely monitor their cardiovascular health over time.
Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients
Somers EC, Zhao W, Lewis EE, Wang L, Wing JJ, Sundaram B, Kazerooni EA, McCune WJ, Kaplan MJ.
PLoS One 7: e37000.