Antiphospholipid Antibodies: It may matter which ones you have
- Arteriosclerosis obliterans associated with anti-cardiolipin antibody/β2-glycoprotein I antibodies as a strong risk factor for ischaemic heart disease in patients with systemic lupus erythematosus
Rheumatology, Volume 47, Number 5, May 2008, pp. 684-689
What is the topic?
One-third of people with lupus test positive for antiphospholipid antibodies (aPLs). The aPLs are a group of antibodies that interact with proteins that regulate blood clotting and blood-vessel stability. These proteins are often found associated with the membranes of cells (thus aPLs target structures which are found on the outside of cells, as opposed to antinuclear antibodies, ANAs, which attach to material from inside the nucleus, or the command center, inside cells).
Some common types of aPLs are: anti-cardiolipin antibodies (aCL); anti-beta-2-glycoprotein I antibodies (anti-β2-GPI); anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT); and lupus anticoagulant (LA), which refers to a way in which some of these antibodies interfere with a blood clotting test.
Antiphospholipid antibodies can interfere with the normal function of blood vessels in various ways, which in turn can lead to complications such as immediate blood clots in arteries or veins, miscarriages, or more long-term damage to blood vessels, including hardening of the arteries (atherosclerosis) and later onset of heart disease and strokes.
What did the researchers hope to learn?
The researchers wanted to see if there were different risks for blood vessel disease depending on whether a person with lupus had aCL/β2-GPI, anti-PS/PT, or LA antibodies.
Who was studied?
The researchers studied blood samples from 155 lupus patients, ranging in age from 8 to 82. Eleven were men; 144 were women. The researchers also studied blood samples from 150 healthy volunteers (62 women, 88 men; age range 21-58 years) to compare with the blood samples from the lupus patients.
How was the study conducted?
The patients were evaluated for risk factors and signs of blood vessel disease, heart disease, and strokes. Twenty-five of the patients (16.1%) were diagnosed with a condition called arteriosclerosis obliterans (ASO); in ASO, fatty deposits called plaque build up along the inside of blood vessel walls, narrowing the opening through which the blood flows. The other 130 patients studied did not have ASO.
Fifteen (9.6%) of the lupus patients had some form of heart disease: 13 had a history of chest pains due to blood vessel blockages in the heart (angina pectoris); and two had suffered full-scale heart attacks. Twenty-five patients (16.1%) had a history of either strokes or ministrokes.
The researchers then compared the levels of different kinds of aPLs among the patients with ASO, heart disease, and strokes or ministrokes.
What did the researchers find?
The researchers found that both aCL and β2-GPI and anti-PS/PT levels were significantly higher in the ASO group than in the ASO-negative group. Using a statistical method that can sort out the overlap among various risk factors, it was found that aCL/β2-GPI, but not anti-PS/PT, was a significant risk for ASO in lupus patients.
Since high cholesterol, high blood pressure, and diabetes have also been reported to contribute to ASO, the researchers examined the presence of these risk factors in the ASO group of lupus patients. They found that none of these traditional risk factors was a reliable risk for ASO. However, this does not rule out their potential contribution to risk since there were only a small number of patients with ASO in this study.
Thirty-six percent of the 25 patients with ASO (9 of 25) also had heart disease, compared to only 4.6 percent (6 of 130) of the ASO-negative patients. There was no significant difference between the two groups when it came to a history of strokes or ministrokes. This suggests that ASO could be a major contributing factor to the development of heart disease in lupus patients.
What were the limitations of the study?
This study establishes an association between aCL/β2-GPI antibodies and ASO, and suggests that ASO could be important in the development of heart disease in lupus patients. However, that does not necessarily mean that having the aCL/β2-GPI antibodies causes ASO, and most people with these antibodies do not have ASO.
A second limitation is how the study was designed. The researchers combined results from a blood test taken at a particular point in time with clinical histories of past medical conditions such as a previous heart attack or stroke. There is no way to be sure that the patient had elevated antibodies at the time the stroke or heart attack occurred.
Finally, given the small numbers of patients with ASO, it is not surprising that this study failed to detect high cholesterol, high blood pressure, and diabetes as risk factors for ASO in lupus patients. However, many other studies have indicated those risk factors are important not only for the public at large but for lupus patients as well.
What do the results mean for you?
aCL/β2-GPI and ASO may help identify lupus patients at higher risk for heart and blood vessel disease who should be considered for preventive treatments and a comprehensive look at other risk factors. People with lupus should be aware that lifestyle changes such as diet and exercise, along with medications to control blood fats and blood pressure, can have a major impact in reducing the risk of heart disease and strokes. Also, the more that is learned about special risk factors in lupus, the better the preventive care will be for all lupus patients.