During eight years of follow-up for more than 1,000 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) registry, 97 vascular events occurred in 72 patients, according to Murray B. Urowitz, MD, of Toronto Western Hospital, and colleagues.
Stepwise multivariate analyses of putative risk factors revealed that only male gender (odds ratio 3.67, 95% CI 1.41 to 9.52) and older age at diagnosis (OR 1.08, 95% CI 1.05 to 1.11) were associated with atherosclerotic vascular events, the SLICC investigators reported online in Arthritis Care & Research.
Several smaller studies have investigated cardiovascular outcomes and risk factors in lupus, but the incidence and prevalence of atherosclerotic events -- and whether the events are attributable to atherosclerosis, lupus itself, or other causes -- remained uncertain.
"To address this complex clinical problem with appropriate epidemiologic tools in a relatively uncommon disease such as [systemic lupus erythematosus] would be impossible without a concerted international effort," the investigators stated.
Consequently, the investigators enrolled 1,249 patients from 26 centers between 2000 and 2008, collecting data on demographics, clinical and laboratory features, risk factors for coronary artery disease (CAD), and outcomes at baseline and annually.
Atherosclerotic events were considered attributable to atherosclerosis if lupus was inactive at the time of the event, if there were typical atherosclerotic changes on angiogram, or if there was evidence of cerebrovascular or peripheral vascular involvement.
Almost 90% of patients were women, and half were white. Mean age at presentation was 34 years, and mean disease duration was 5.5 months.
Most patients were already receiving therapy with corticosteroids and antimalarial drugs at baseline.
Cardiovascular events included 13 cases of myocardial infarction, 15 of angina, 24 of congestive heart failure, one pacemaker insertion, and eight cases of peripheral vascular disease.
Cerebrovascular events included 13 transient ischemic attacks and 23 strokes.
Of the 97 events, the researchers attributed only 31 (in 22 patients) to atherosclerosis, while 50 were attributed to active lupus and 16 to other causes. The events occurred a mean of two years after enrollment -- very early in the course of disease.
Males comprised only 11.7% of the cohort but were 41% of the patients who had atherosclerotic events (P<0.0001), Urowitz and colleagues indicated.
Compared with patients without events, patients with events also were characterized by:
- Older age at diagnosis, 54.6 years versus 34.6 years (P<0.0001)
- Caucasian race, 77.3% versus 53.3% (P=0.03)
- Hypertension, 73.6% versus 32.3% (P=0.002)
- Obesity, 57.1% versus 28.1% (P=0.004)
- Smoking, 63.6% versus 36.6% (P=0.01)
- Family history of CAD, 42.9% versus 20% (P=0.02)
Race, family history, and traditional risk factors were no longer significant, however, in the multivariate analysis.
When patients with events attributable to atherosclerosis were compared with patients whose vascular events were associated with lupus, associations were seen for:
- Male gender, 40.9% versus 19.1% (P=0.06)
- Older age at diagnosis, 54.6 years versus 41.2 years (P=0.0004)
- Caucasian race, 77.3% versus 50.0% (P=0.03)
- Use of antimalarials at baseline, 72.7% versus 36.6% (P=0.006)
In discussing their findings, the investigators noted the lack of association for traditional Framingham risk factors with atherosclerotic vascular events.
A possible explanation may be the short duration of disease at entry -- less than 15 months -- which may have reduced the impact of risk factors.
"It is possible that over time these risk factors will exert their influence," Urowitz and colleagues wrote.
"In early disease it is likely that male gender and older age states associated with increased risk factors for atherosclerotic vascular events are dominant. This should not deter from the necessity for aggressive intervention in the treatment of classic CAD risk factors," they said.
An important feature of this study, according to the investigators, was its effort to clarify whether events were attributable to atherosclerosis. They advised other clinicians and researchers to do the same.
"In patients with known atherosclerotic disease, active lupus may make the attribution of an event more difficult, and in cases of active lupus, subclinical atherosclerosis may be missed."
However, in most cases the attribution rules followed in this study helped clarify the findings, they asserted.
Limitations of the study included its relatively short duration and the small number of events and male participants. Strengths were the size of the inception cohort, its multiethnic composition, and uniform collection of data.
The patients in the SLICC cohort will continued to be followed for five years.
The SLICC investigators were supported by multiple sources, including the Canadian Institutes of Health Research, Lupus UK, the Lupus Foundation of America, the Arthritis Research Campaign, the Fonds de la Recherche en Sante du Quebec, the Hopkins Lupus Cohort, and the National Institutes of Health.
No potential conflicts of interest were reported.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner