IgG Antiphospholipid Antibodies Commonly Overlooked Finding in Heart Attack Patients

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 IgG ANTIPHOSPHOLIPID ANTIBODIES COMMONLY OVERLOOKED FINDING IN HEART ATTACK PATIENTS

Newswise — CHICAGO – According to new research findings presented this week at the ACR/ARHP Annual Meeting (Abstract #855), IgG antiphospholipid antibody positivity and myocardial infarction (MI) also known as a heart attack – are strongly and independently associated, suggesting it may be an important, often-overlooked risk factor for heart attack in the general population.

Antiphospholipid syndrome (APS) – also called antiphospholipid antibody syndrome – is an autoimmune disease that most often affects young women. Patients with APS make abnormal proteins called antiphospholipid autoantibodies (aPL) in the blood. These antibodies target proteins in the circulation and in cellular membranes, and some of them have the ability to interfere with the blood clotting system. People with APS may otherwise be healthy, but many also suffer from another underlying rheumatic disease, most frequently systemic lupus erythematosus (SLE).

 APS is present when arterial, venous or microvascular thrombosis or obstetric morbidity occur with confirmed, positive blood tests for aPL. Long-term anticoagulation treatment prevents new thrombotic events in most APS patients. However, there is still conflicting information about the occurrence of pro-thrombotic aPL in unselected myocardial infarction (MI) cases, due to limited size, selected populations and/or non-standardized methods in previous studies.

The study conducted by researchers in Sweden was designed “to shed light on the role of aPL in patients with MI,” said Elisabet Svenungsson, MD, Senior Consultant, Professor of Rheumatology at Karolinska Institutet/Karolinska University Hospital and the study’s co-author. “It used standardized methods for aPL determination and explored the prevalence of aPL (anti-cardiolipin and/or anti-β₂glycoprotein-I antibodies) in a large cohort of well-characterized patients with a first-time MI and in age- and gender-matched population controls.”

The study participants were divided into two groups: 805 patients less than 75 years old were investigated six to 10 weeks after a first-time MI, and 805 age-, sex- and area-matched controls who were MI-free. Using paired statistical analyses, the researchers looked for associations between aPL positivity (including anti-cardiolipin (aCL), anti-β₂glycoprotein-I (anti-β₂-GPI), IgG, IgM and IgA) and MI. In addition, aPL-positive myocardial infarction patients and six previously diagnosed APS patients were tested on a peptide ELISA regarding reactivity to specific domains of the β₂GPI protein, believed to be the main antigen for aPL.

According to the study’s results, 10.9 percent of MI patients were positive for IgG anti-CL versus 0.9 percent of the controls, and 10.4 percent of MI patients were positive for anti-β₂GPI compared to 0.9 percent of controls. Many of the myocardial infarction patients in the study also had high IgG titers. IgG positivity for anti-CL and anti-β₂-GPI was highly correlated, and these antibodies were therefore evaluated together as combined aPL IgG positivity.

Using this definition, aPL IgG positivity remained associated with myocardial infarction after adjusting for traditional cardiovascular risk factors like smoking, hypertension, diabetes and body-mass index. The researchers also report that anti-β₂GPI antibodies from myocardial infarction patients usually recognized one domain of the β₂-GPI protein, while antibodies from the APS patients targeted several domains.

The findings suggest IgG positivity is strongly and independently associated with MI. This suggests that IgG aPL positivity could be an important, but neglected, risk factor present in one out of ten MI patients in the general population, the researchers concluded.

“We are now conducting longitudinal studies which address two remaining pivotal questions: If the observed aPL IgG in patients with MI are persistent or transient, and if the prognosis of MI patients who are aPL IgG differs compared to other MI patients,” said Dr. Svenungsson. “If our results and hypotheses are confirmed, aPL testing may become part of routine MI care, and help identify MI patients who are at high risk for complications and who may benefit from anticoagulation treatment as protection from future vascular events.”

About the ACR/ARHP Annual Meeting

The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. With more than 450 sessions and thousands of abstracts, if offers a superior combination of basic science, clinical science, tech-med courses, career enhancement education and interactive discussions on improving patient care. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official #ACR18 hashtag.

 About the American College of Rheumatology

The American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit www.rheumatology.org.

IgG Antiphospholipid Antibodies, -a Common but Neglected Finding in Patients with Myocardial Infarction

Giorgia Grosso¹, Natalie Sippl², Barbro Kjellström³, Khaled Amara², Ulf de Faire², Kerstin Elvin⁴, Bertil Lindahl⁵, Per Näsman⁶, Lars Ryden², Anna Norrhammar⁷ and Elisabet Svenungsson⁸, ¹Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, ²Karolinska Institutet, Stockholm, Sweden, ³Cardiology Unit, Department of Medicine Solna, Stockholm, Sweden, ⁴Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ⁵Uppsala University, Uppsala, Sweden, ⁶KTH Royal Institute of Technology, Stockholm, Sweden, ⁷Capio S:t Görans hospital, Stockholm, Sweden, ⁸Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden

Background/Purpose: The antiphospholipid syndrome (APS) is present when arterial, venous or microvascular thrombosis or obstetric morbidity concur with confirmed positive tests for antiphospholipid antibodies (aPL). Long-term anticoagulation prevents new thrombotic events in most APS patients. Information on the occurrence of pro-thrombotic aPL in myocardial infarction (MI) is conflicting due to limited size, selected populations and/or non-standardized methods in previous studies.

Methods: 805 patients (age <75 years; 6-10 weeks after a first MI) and 805 age- (mean 62± 8 years), sex- (male 81%) and area-matched controls, free from MI, were examined. Associations between aPL positivity [anti-cardiolipin (aCL) and anti-β₂glycoprotein-I (anti-β₂GPI), IgG, IgM and IgA] and MI were studied by paired statistical analyses (paired Student’s t-test, McNemar´s test). Additionally, aPL positive MI patients and 6 APS patients, defined according to the Sydney criteria, were tested on a peptide ELISA regarding reactivity to specific domains of the β₂GPI protein.

Results: Positivity for IgG anti-CL and IgG anti-β₂GPI was noted in 10.9% versus 0.9% [p<0.0001 ] and in 10.4% versus 0.9% [p<0.0001) among MI patients and controls respectively, and many MI patients had high IgG titers. aPL of IgM and IgA isotypes did not differ (figure). IgG positivity for anti-CL and anti-β₂GPI was highly correlated (r_Spearman=0.85) and these antibodies were therefore evaluated combined as aPL IgG positivity (n=88). Using this definition aPL IgG positivity remained associated with MI after adjustment for traditional cardiovascular risk factors (present smoking, hypertension, diabetes and body mass index) [adjusted OR 8.9 (95%CI: 4.6-17.3)]. Anti-β₂GPI antibodies from MI patients usually recognized one domain of the β₂GPI protein, while antibodies from APS patients targeted several domains.

Conclusion: In a large representative cohort of patients with a first-time MI and matched controls, we report a strong independent association between IgG aPL positivity and MI, suggesting that IgG aPL could be an important risk factor for MI in the general population. If long-term cohort studies can confirm causality for IgG aPL, our results may alter handling, treatment and outcomes for many patients with MI.

Disclosures: G. Grosso, None N. Sippl, None B. Kjellström, None K. Amara, None U. de Faire, None K. Elvin, None B. Lindahl, None P. Näsman, None L. Ryden, None A. Norrhammar, None E. Svenungsson, None