TOPIC SERIES: CVD PREVENTION IN RHEUMATIC DISEASE

Some patients with lupus may experience myocardial infarction (MI) before being diagnosed with systemic lupus erythematosus (SLE), according to data recently published in Lupus Science & Medicine. The findings suggest that there may be a link between autoimmune inflammation and atherosclerosis.

The systemic lupus international collaborating clinics (SLICC) group developed an international registry of newly diagnosed patients with SLE to determine the incidence, prevalence, and nature of atherosclerotic coronary artery disease in SLE. Using the data from the registry, researchers sought to describe the frequency of MI prior to the diagnosis of SLE and within the first 2 years of follow-up.

The SLICC atherosclerosis inception cohort included 1848 patients who had first been diagnosed with 4 or more American College of Rheumatology criteria for the classification of SLE within the past 15 months. The researchers recorded rates of MI, which were reported and attributed on a specialized vascular event form. All MIs were confirmed by abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes, or an abnormal stress test, echocardiogram, nuclear scan, or angiogram.


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A total of 31 patients experienced an MI, 23 of whom had a prior MI before an SLE diagnosis or within 2 years after the diagnosis. Of these 23 patients, 60.9% were female, 78.3% were Caucasian, 8.7% were black, 8.7% were Hispanic, and 4.3% were “other.”

The average age at SLE diagnosis was 52.5 ± 15.0 years. Among the 23 patients who experienced a prior MI before SLE diagnosis, 16 MIs occurred at a mean of 6.1 ± 7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up.

Patients who experienced an MI were more likely to be male, white, and be diagnosed at an older age. They were more likely to have hypertension (HTN), hypercholesterolemia, and a family history of MI or smoking. The researchers noted that only age (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.03-1.09), HTN (OR: 5.09; 95% CI: 1.34-18.23), hypercholesterolemia (OR: 4.43; 95% CI 1.51-12.99), and smoking status (OR: 7.50; 95% CI: 2.38-23.57) were independent risk factors for the development of early MI.

According to the authors, these results highlight a possible relationship between immunologic and inflammatory mechanisms that can cause both SLE and atherosclerosis. “The physician caring for patients with SLE must be aware that these patients require careful investigation and treatment of cardiovascular risk factors,” they noted.

The researchers raise the question as to defining the interplay between SLE disease activity and atherosclerotic events.  They state that autoantibodies formed many years prior to SLE disease diagnosis result in subclinical autoimmunity which then leads to subclinical atherosclerosis, and that initial clinical presentation could be either atherosclerosis or SLE.  However it is also possible that both autoimmunity and atherosclerosis independently develop, with varying times of clinical manifestation secondary to genetic predisposition or environmental influences. 

With regards to how to mitigate cardiovascular risk factors in patients with SLE, study co-author M.B. Urowitiz, MD, Director of the Centre for Prognosis Studies in the Rheumatic Diseases and Professor of Medicine at the University of Toronto, told Rheumatology Advisor that  “SLE patients in general should have the classic risk factors monitored regularly and treated early”.

Of interest is the finding that after multivariate analysis, anticardiolipin antibodies, lupus anticoagulant, and family history of MI at study inception were all not significantly associated with increased risk for developing MIs early in lupus disease course.

Summary and Clinical Applicability

Because of the potential association between SLE and atherosclerosis, physicians should be aware that patients with SLE should be closely monitored for possible cardiovascular risk factors.

“Physicians caring for patients with premature atherosclerotic disease should consider the possibility of an increased risk of autoimmune disease and consider investigating such patients for ‘benign autoimmunity’ that is the presence of autoantibodies in the absence of any clinical disease with an autoantibody screen,” the authors concluded. 

Limitations and Disclosures

The authors note that a universal definition of MI criteria was unavailable at the time that the cohort was developed. Because the cohort was collected to discern atherosclerotic cardiovascular events in lupus patients, the researchers excluded lupus disease activity when attributing a cardiovascular event to atherosclerosis.

The study was funded by the Canadian Institutes of Health Research, Lupus UK, Tolfo Family, Lupus Ontario, and the Conn Smythe Foundation.

Reference

Urowitz MB, Gladman DD, Anderson NM, et al. Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort. Lupus Sci Med. 2016;3(1):e000143.