Antiphospholipid antibodies indicate higher risk for future cardiovascular events
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Key takeaways:
- The presence of antiphospholipid antibodies independently predicted future atherosclerotic cardiovascular disease events.
- The researchers noted that future research may help to determine the extent to which therapeutic strategies may mitigate these risks.
Anticardiolipin IgA and a2GPI IgA positivity, together at a single time point, indicate an increased risk for future atherosclerotic cardiovascular disease events, according to data published in JAMA Network Open.
“Although patients with autoimmune diseases have long been known to have heightened atherosclerosis cardiovascular disease (ASCVD) risk, the impact of autoimmunity on this risk in the general population remains unknown,” Yu Zuo, MD, MSCS, of the division of rheumatology at the University of Michigan, told Healio. “Whether various antiphospholipid antibodies (aPL), particularly those newer non-criteria aPL that are not usually considered clinically, can be detected in ethnically diverse healthy individuals and affect their future health has not been previously investigated.”
To investigate the link between aPL at a given time point and future ASCVD events, Zuo and colleagues conducted a cohort analysis using data from the Dallas Heart Study. None of the participants self-reported autoimmune disease requiring immunosuppressive medication, and participants were free of ASCVD events.
Antiphospholipid antibodies and antinuclear antibodies were measured from plasma. ASCVD events were defined as the first nonfatal myocardial infarction, first nonfatal stroke, coronary or peripheral artery revascularization, or cardiovascular death. Additionally, the researchers measured two markers indicating neutrophil extracellular trap remnants. These were myeloperoxidase-DNA complexes and citrullinated histone H3. All samples were collected between 2007 and 2009.
The analysis included 2,427 participants. Antiphospholipid antibodies were present at a single time at a rate of 14.5%. According to the researchers, approximately one-third of those patients demonstrated antibodies at a “moderate” or “high” titer. The antibody that was most common was the anticardiolipin IgA, which was present in 156 patients (6.4%). The presence of anticardiolipin IgA (HR = 4.92; 95% CI, 1.52-15.98) and a2GPI (HR = 2.91; 95% CI, 1.32-6.41) were both individually linked to future ASCVD events.
“After adjusting for age, sex, race, ethnicity, BMI, smoking history, systolic blood pressure, diabetes, total cholesterol, HDL, eGFR, medications and multiple comparisons, positive testing for aCL IgA and a2GPI IgA at a single time point were each significantly associated with future ASCVD events,” Zuo said. “Our data support that some aPL may be important cardiovascular disease risk-enhancers. Although further studies are needed, testing some aPL, including non-criteria aPL, may lead to improved risk stratification and prevention for ASCVD in the general population.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
In rheumatology, we are frequently faced with patients with autoantibodies. We know that autoimmunity precedes autoimmune disease — this has been shown by the group in Oklahoma and others. When we see a patient with autoantibodies, the question is always, “Does this represent a disease or is it ‘false positive?’” Is this background noise that has no clinical significance, or could it be the forerunner of future disease and tissue damage?
The present investigation, using the Dallas Heart Study, performed antiphospholipid antibody (aPL) serology and then followed for the occurrence of atherosclerosis cardiovascular disease (ASCVD).
Their data suggest that the presence of certain aPL, particularly the IgA isotypes of aCL and aβ2GPI, even when measured at a single time point, are associated with future ASCVD events. This is quite remarkable in the context of the thinking that autoantibodies are mainly “false positive” and of no clinical significance.
Further studies need to be done to confirm these findings. The rheumatology consults for a cardiovascular event associated with positive aPL antibodies will have us more aware that this doesn’t have to be catastrophic antiphospholipid syndrome to be significant.
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