Atherosclerotic Events on the Decline in SLE Save

The prevalence of atherosclerotic vascular events among patients with systemic lupus erythematosus (SLE) today is considerably lower than in the past, analysis of multicenter data found.

Among patients enrolled in an inception cohort from 1999 to 2017, only 3.6% of patients had an atherosclerotic vascular event, at a rate of 4.6 per 1,000 patient-years, according to Murray B. Urowitz, MD, of the University of Toronto in Canada, and colleagues.

In contrast, in an analysis of patients with SLE from 1970 to 2004, also by Urowitz's group, approximately 10% of patients experienced an atherosclerotic vascular event during 9 years of follow-up.

"We hypothesize that more effective control of lupus disease activity and treatment of classic atherosclerotic risk factors may have both contributed to controlling atherosclerotic vascular events in this inception cohort," Urowitz and colleagues wrote in their new study, online in Arthritis & Rheumatology.

In recent years, evidence for the excess cardiovascular risk among women with SLE has led to intensive efforts to address traditional risk factors such as dyslipidemia and hypertension. There also has been an increased awareness of the cardioprotective benefits of antimalarial medications.

The Systemic Lupus International Collaborating Clinics (SLICC) inception cohort has enrolled almost 2,000 patients from multiple centers, following them for a mean of 8.3 years. To provide an updated picture of the risks of atherosclerotic vascular events among SLE patients, the investigators analyzed outcomes for 1,710 patients in the SLICC cohort who had at least one follow-up visit and who represented 13,366 patient-years of follow-up.

The outcomes of interest were myocardial infarction, angina, transient ischemic attack, stroke, congestive heart failure, bradyarrhythmia requiring pacemaker insertion, and peripheral vascular disease. Only events occurring during inactive disease (SLE Disease Activity Index of zero) were included, to differentiate events associated with atherosclerosis from those related to the SLE itself.

Patients' mean age at the time of SLE diagnosis was 35, and mean disease duration at the time of SLICC enrollment was 5.7 years. Almost 90% were women, and the majority were white. About 36% of the patients had ever tested positive for anti-cardiolipin (aCL) antibodies or lupus anticoagulant (LA).

Of the 1,710 patients included in the analysis, 85 have died, for a mortality rate of 5%, or 6.4 per 1,000 patient-years.

During follow-up, there were 170 vascular events reported in 113 patients, 86 of which were considered atherosclerotic, with the remainder attributed to SLE itself and other causes such as chronic renal disease and vascular malformations.

Of those 86 events, 61 were first events and 25 were recurrent, with the most common being angina and myocardial infarction. The mean time from diagnosis to a first event was 6 years.

The investigators next considered potential predictors for a first event, and after adjustment for other vascular events on a univariate analysis, they found evidence for these factors as being protective:

• Female sex, HR 0.53 (95% CI 0.29-0.97, P=0.04) 
• Never having smoked, HR 0.46 (95% CI 0.22-0.95, P=0.04)
• Use of antimalarials, HR 0.51 (95% CI 0.30-0.o87, P=0.01)

In contrast, ever having been positive for aCL antibodies or LA was associated with twice the risk for a first atherosclerotic event (HR 2.09, 95% CI 1.18-3.71, P=0.01).

They then performed two multivariate analyses: one which did not include the variable of aCL/LA, which was missing in a sizeable number of patients, and the second, which included this variable.

In the model that excluded aCL/LA, factors that were associated with an increased risk of first atherosclerotic event were prior vascular events (HR 4.0, 95% CI 1.55-10.3, P=0.004) and body mass index of 40 or higher (HR 2.74, 95% CI 1.04-7.18, P=0.04), while antimalarial use was protective (HR 0.54, 95% CI 0.32-0.91, P=0.02).

Similar results were seen in the model that included aCL/LA, with increased risk being associated with prior vascular events (HR 4.76, 95% CI 1.80-12.60, P=0.002) and BMI of 40 or higher (HR 3.10, 95% CI 1.17-8.23, P=0.02), and antimalarial use being protective (HR 0.52, 95% CI 0.29-0.92, P=0.02).

The decreased rate of atherosclerotic events seen in this analysis is similar to what has been seen in the general population in recent years, and also reflects improved SLE disease control and less reliance on glucocorticoids.

In addition, "in all our analyses we found that antimalarial treatment was protective for atherosclerotic vascular events, emphasizing the importance of this therapy in the management of SLE," the authors concluded.

A limitation of the study, they noted, was the possibility of some inaccuracies in the determination of whether the events were atherosclerotic or not, as these judgments were made by the local investigators.

Disclosures

The authors reported support from the Canadian Institutes of Health, Lupus UK, Andwell and West Birmingham Hospitals NHS Trust, the National Institute for Health Research/Wellcome Trust, the National Institutes of Health, the Singer Family Fund for Lupus Research, Arthritis Research UK, the Danish Rheumatism Association, the Novo Nordisk Foundation, the Department of Education, Universities and Research of the Basque Government, and the National Institute for Health Research University College London Hospitals Biomedical Research Center.

Arthritis & Rheumatology: Urowitz MB, et al "Accrual of atherosclerotic vascular events in a multicenter inception SLE cohort" Arthritis Rheum 2020; DOI: 10.1002/art.41392.