A team of researchers in Canada has found a 7.4-fold higher risk for an incident stroke in the first year after diagnosis of systemic lupus erythematosus (SLE) compared with healthy controls, in a population-based study.

The researchers, from Toronto, further found that a high percentage of lupus patients’ resting electrocardiograms (ECGs) are abnormal. The results of both studies were presented at the Canadian Rheumatology Association’s 2014 annual meeting, held recently in Whistler, British Columbia.

Antonio Avina-Zubieta, MD, PhD, the British Columbia Lupus Society Scholar, said the spike in stroke risk immediately after diagnosis “is a new finding—to the best of my knowledge, nobody has reported this.” His team also uncovered a 2.7-fold overall higher risk for stroke in people with SLE and a sixfold elevated risk for stroke in patients under the age of 45 years. This should put physicians on high alert for cerebrovascular symptoms in lupus patients, especially younger or newly diagnosed individuals, he noted.

Sasha Bernatsky, MD, PhD, who was not involved in either study, said she and her colleagues previously presented a study of administrative data, from Quebec, showing a higher risk for stroke in patients with systemic vasculitis, a similar disease (American College of Rheumatology 2013 annual meeting; Arthritis Rheum 2013;740:S312). She also led a study that showed a doubling of lupus patients’ death rate from cerebrovascular disease (Lupus 2006;15:835-839).

“There are good reasons for patients with serious rheumatic diseases like SLE to have a family physician who can properly co-manage their risk factors for stroke, such as high blood pressure, smoking and so on,” Dr. Bernatsky wrote in an email exchange with Pain Medicine News. Dr. Bernatsky is an associate professor in the Department of Medicine, Divisions of Rheumatology and Clinical Epidemiology, McGill University Hospital in Montreal.

She also noted that, in fact, the Toronto team is now leading an international analysis of a very large cohort of patients with new-onset SLE “to clarify the issue of ECG changes in SLE, and to determine the optimal way to monitor these patients.”

Dr. Avina-Zubieta, who also is assistant professor of medicine, University of British Columbia, and a research scientist at the Arthritis Research Centre of Canada, in Vancouver, and his colleagues searched for individuals with a diagnosis of SLE in the province’s Medical Services Plan made during 1990-2010. They defined SLE diagnosis as a non-rheumatologist recording two or more relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes at least two months apart but within a two-year period; or a rheumatologist recording at least one relevant ICD-9 code or at least one ICD-9 or ICD-10 code during a hospitalization. New SLE cases were required to not have an ICD-9 or ICD-10 code for SLE recorded between 1990 and 1995.

The investigators also performed some of the analyses with a stricter definition of SLE, which included the criterion of use of oral glucocorticosteroids, antimalarials, immunosuppressive drugs or methotrexate from one month before to six months after diagnosis. In addition, they identified 10 control subjects matched on age, sex and calendar year from the general population for each SLE case from the database. This yielded 4,972 SLE cases and 49,976 matched controls.

As expected, lupus patients had poorer overall health status, including higher rates of risk factors for cerebrovascular accidents (CVAs), such as angina, and significantly higher rates of use of glucocorticosteroids, statins and fibrates at the time of diagnosis, than the controls.

Dr. Avina-Zubieta’s team performed a multivariable analysis and found a 2.7 relative risk for a CVA compared with controls. This was slightly lower but still statistically significant, with a 2.2 relative risk, when researchers used the stricter SLE definition. The relative risk also remained high when the researchers adjusted for potential unmeasured confounders in sensitivity analyses. Furthermore, the risk was much higher immediately after diagnosis of SLE, with an incidence rate ratio of 7.4 in the first year, falling to 1.2 after five or more years after diagnosis.

“This is the novel finding in the study; it suggests a role of inflammation in the pathogenesis of stroke in these patients,” Dr. Avina-Zubieta said.

Women had a higher relative risk than men, and people aged 45 years or younger were also at a sharply higher risk for a CVA.

The study was funded by the Canadian Arthritis Network, the BC Lupus Society and the Canadian Institutes for Health Research.

The presentation on resting ECG abnormalities focused on 274 consecutive patients visiting the Toronto Lupus Clinic at the University Health Network between October 2012 and May 2013. The average disease duration was 17 years, and 40.5% of the patients had an abnormal 12-lead resting ECG. Lead author Zahi Touma, MD, PhD, and his co-investigators found that these included ST-segment and/or T-wave abnormalities (19.7% of patients), arrhythmia (11.7%), atrial enlargement (2.6%) and left bundle branch block (0.4%). These changes are all associated with a significantly elevated risk for subsequent cardiovascular events.

—Rosemary Frei, MSc


Drs. Avina-Zubieta, Bernatsky and Touma did not disclose any relevant conflicts of interest.