CV Events Strike Early in Lupus Save

Patients with systemic lupus erythematosus are at risk of cardiovascular events early in the course of disease -- and even before their lupus is diagnosed, an international study found.

In the Systemic Lupus International Collaborating Clinics (SLICC) atherosclerosis inception cohort, 31 of 1,848 patients had a myocardial infarction (MI) during a mean follow-up of 8.9 years. And in 23 of those patients, the MIs occurred either before they were diagnosed with lupus or within 2 years of diagnosis, according to Murray B. Urowitz, MD, of the University of Toronto, and colleagues.

A total of 16 of the MIs occurred at a mean of 6.1 years before the lupus diagnosis, while seven were within the first 2 years of disease, the researchers reported in Lupus Science & Medicine.

It has been well recognized that patients with lupus are at risk for cardiovascular disease. However, the mortality pattern has been reported as being predominantly related to lupus itself and infection early in disease, with cardiovascular causes being more common in later disease.

However, a recent study observed an increase in cardiovascular events in the years prior to lupus diagnosis, raising the question of whether the reason was delayed diagnosis of lupus or accelerated atherosclerosis prediagnosis.

To address this, Urowitz and colleagues analyzed data from the SLICC cohort, a prospective, longitudinal study that enrolled patients from 2000 to 2014 shortly after diagnosis, following them to establish the incidence and risk factors for coronary artery disease over time.

Patients were seen at yearly intervals, with assessment of clinical and laboratory features as well as medical history, risk factors, and comorbidities.

Of the 1,848 participants, 89% were women, mean age at diagnosis was 35, and mean disease duration at the time of enrollment was 6 months.

Among the 23 patients who had an MI, 14 were women, 18 were Caucasian, two were of African descent, two were Hispanic, and one was "other." The mean age at MI was 49.

When patients with early MI were compared with the larger SLICC cohort, risk factors included male sex, older age, Caucasian ethnicity, hypertension and dyslipidemia, smoking, and family history of MI.

There also were no differences in serology, including anticardiolipin or lupus anticoagulant, in acute phase reactants, or in lupus medications including steroids.

In a univariate analysis, factors associated with early MI were hypertension, with an odds ratio of 7.55 (95% CI 2.56-22.27), ever smoking (OR 6.85, 95% CI 2.53-18.52), hypercholesterolemia (OR 5.91, 95% CI 2.17-16.10), male sex (OR 5.25, 95% CI 2.25-12.29), Caucasian race (OR 3.77, 95% CI 1.39-10.19), family history of MI (OR 2.02, 95% CI 1.03-3.99), and age (OR 1.08, 95% CI 1.05-1.11).

After controlling for disease activity, low complement levels, and steroid use, a multivariate analysis found these independent associations with early MI:

• Smoking, OR 7.50 (95% CI 2.38-23.57);
• Hypertension, OR 5.09 (95% CI 1.34-18.23);
• Hypercholesterolemia, OR 4.43 (95% CI 1.51-12.99); and
• Age, OR 1.06 (95% CI 1.03-1.09).

The authors noted, "It is interesting that anticardiolipin antibodies, lupus anticoagulant, and family history of all MIs at inception were not significantly associated factors in the multivariate analysis." One previous study found a strong association for the presence of anticardiolipin antibodies and first cardiovascular events in patients with lupus, while another found that MI was significantly more common among patients with lupus anticoagulant.

A total of 17 of the patients who had MIs were age 40 to 49, giving a prevalence of 4.8%, compared with a prevalence of 0.7% among that age group in the wider population of Ontario.

In addition, 15 patients developed angina, with five during the first 2 years after lupus diagnosis, and were considered as being at risk for subsequent MI.

In discussing the findings, Urowitz and colleagues said they considered the relationship between lupus and atherosclerotic events, noting that pathogenic mechanisms are at work for years before clinical events. For lupus, autoantibodies appear long before clinical onset of disease, indicating a state of subclinical autoimmunity.

And for atherosclerotic events, metabolic and inflammatory processes are common precedents to clinical disease.

"It is therefore possible that subclinical autoimmunity may result in subclinical atherosclerosis and either can manifest itself clinically as the initial clinical presentation. Alternatively, the two mechanisms -- autoimmunity and atherosclerosis -- may develop independently but concurrently and may manifest themselves clinically at different times," the researchers explained.

The relationship may involve genetic factors as well as environmental and epigenetic influences, they noted.

These findings highlight the importance for clinicians to be attentive to cardiovascular risk factors in patients with lupus. "Also, 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,'" the researchers wrote.

A limitation of the study was that the current definition of MI criteria was not yet available when the SLICC cohort was initiated, and the World Health Organization criteria were used.

--Nancy Walsh, Senior Staff Writer, MedPage Today

The study was supported by the Candadian Institutes of Health Research, Lupus UK, the Tolfo family, Lupus Ontario and the Conn Smythe Foundation.

This is brought to RheumNow readers by our friends at MedPage Today. It was originally published April 13, 2016.