Antiphospholipid Antibody Linked to First MI

Patrice Wendling

October 23, 2018

CHICAGO — Anticardiolipin antibodies targeting immunoglobulin G (IgG) are common in patients surviving a first myocardial infarction (MI) and occur independent of traditional cardiovascular risk factors, a new study suggests.

"These findings are surprising, and they're also very clear and very strong," lead author Elisabet Svenungsson, MD, PhD, Karolinska Institute, Stockholm, Sweden, told theheart.org | Medscape Cardiology. "For the future, I think we need to look at temporal relationships between these antibodies and events."

Because antiphospholipid antibodies (aPLs) can come and go or increase and decrease, "it could be that the antibodies are a reaction to the tissue damage of the MI since the blood samples were taken 6 to 10 weeks after the infarction," she said.

Still, the presence of aPLs, such as anticardiolipin or anti-beta2 glycoprotein 1 (anti-β2GPI), predisposes patients to blood clots. Patients diagnosed with antiphospholipid syndrome (APS) are also at risk of valvular abnormalities.

Small sample sizes, selected populations, and nonstandardized testing, however, have produced conflicting results on the occurrence of aPLs in MI, said Svenungsson, who presented the results here at the American College of Rheumatology (ACR) 2018 Annual Meeting to coincide with publication in Annals of Internal Medicine.

To assess the frequency of anti-β2GPI, anticardiolipin isotopes, and antinuclear antibodies in MI, researchers examined 805 consecutive patients younger than 75 years (mean, 62 years; 81% male) hospitalized for a first MI at 17 hospitals in Sweden between 2010 and 2014 and 805 controls matched for age, sex, and region in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study.

Patients with MI were trend-wise more likely to be current smokers (26% vs 12%), have any rheumatic disease (11% vs 7%), and have chronic pulmonary obstructive disease (4% vs 2%).

Patients with MI were more likely than controls to have IgG anticardiolipin (11% vs 1%; P < .001) and IgG anti-β2GPI antibodies (10% vs 1%; P < .001), whereas IgA and IgM antibodies were not significantly different between groups.

"The IgG findings are very interesting I think since they are so consistent" but "we don't really understand this," Svenungsson said. "In rheumatology, what we know is that IgG antibodies, as compared to IgM and IgA, are more strongly associated with the events included in the definition of APS, that is venous, small vessel, and arterial thrombosis and pregnancy morbidities."

"But we don't really know the temporal relationship between antibodies and events and if there is a class that switch from IgM to IgG, like you see in infections. So I think this is a very important question to pose to investigators."

Notably, age did not differ between patients with MI who were aPL IgG-positive and IgG-negative (63.1 years vs 61.8 years), although IgG-positivity trended higher in women (26.1% vs 17.9%) and current smokers (33.7% vs 25.1%).

On multivariate analysis, IgG positivity (odds ratio [OR], 7.8; 95% CI, 4.0 - 15.3) and current smoking (OR, 2.6; 95% CI, 1.9 - 3.5; both P < .001) remained associated with MI, whereas diabetes, hypertension, and body mass index did not.

The researchers also tested aPL-positive MI patients and six APS patients, defined according to the Sydney criteria, for specific domains of the β2GPI protein. Those results showed that patients with MI had antibodies to fewer domains, mainly domains IV and V, while antibodies from patients with APS targeted several of the plasma protein's five domains.

"It could be an early reaction or it could be an isotype spread like you see with anti-citrullinated antibodies in rheumatoid arthritis with antibodies, but again we don't know," Svenungsson said.

"I think these findings are very interesting but they also pose a lot of new questions. Questions regarding the temporal relationship between antibodies and domains; regarding the isotopes IgG, IgA, and IgM; regarding, of course, if there is a causal relationship to myocardial infarction," she said. "That's the major question and, if so, then if every 10th person with a myocardial infarction in the general population has these antibodies, maybe we can help with anticoagulation."

Direct-acting or novel oral anticoagulants (DOACs/NOACs) have altered treatment for many patients with atrial fibrillation and venous thrombosis, but it is unclear how they compare against warfarin, the gold standard for lifelong anticoagulation in patients with APS.

The recent Rivaroxaban in Thrombotic Antiphospholipid Syndrome (TRAPS) trial (Blood. 2018;132:1365-1371) in high-risk APS patients triple-positive for lupus anticoagulant, anticardiolipin, and anti-β2GPI antibodies was terminated prematurely because of excess arterial events with rivaroxaban compared with warfarin (12% vs 0%), she noted.

Bio-Rad provided reagents for the study but had no influence on study design or analysis. Svenungsson has reported no relevant financial relationships.

Ann Intern Med. Published online October 23, 2018. Abstract

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