Lupus Patients See More Vascular Risk, but It’s Modifiable

Atherosclerosis progression was more than twice as common in younger people with systemic lupus erythematosus (SLE) than in healthy controls in a prospective study from Greece, but the rate difference narrowed substantially with sustained SLE remission and conventional cardiovascular risk factor management.

Among 95 SLE patients and 71 age- and sex-matched healthy individuals followed for 10 years, 52 of the patients and 21 of the controls showed atherosclerotic plaques on carotid ultrasound at the last follow-up, according to Maria Tektonidou, MD, of National and Kapodistrian University of Athens, and colleagues.

That worked out to an incidence rate ratio of 2.26 (95% CI 1.34-3.81, P=0.002), the researchers reported in Arthritis & Rheumatology. Cardiovascular events were also significantly more common among patients (eight vs one among controls).

Achievement of risk-reduction targets for standard factors, however, was associated with a 32% decrease in likelihood of atherosclerotic plaque progression (IRR 0.68, 95% CI 0.53-0.89, P=0.004) for each of five targets attained. These covered blood pressure, lipid levels, smoking, physical activity, and body weight and size.

And staying in remission for at least 75% of the follow-up period was associated with a 43% reduction in risk of atherosclerosis progression (IRR 0.57, 95% CI 0.34-0.95, P=0.033).

“Our findings showed that sustained CVRF [cardiovascular risk factor] control and prolonged clinical remission can substantially reduce atherosclerosis progression risk in SLE, highlighting the need for consistent efforts to achieve both targets in this high-risk young adult population,” Tektonidou and colleagues wrote.

The study initially included a total of 115 SLE patients and 115 controls, with median age 43 at baseline. Follow-up visits were scheduled at years 3, 7, and 10. However, not all participants had carotid ultrasound to assess presence of atherosclerosis. These were missed at year 3 in four patients and 21 controls. Additional withdrawals including three deaths further reduced the numbers available for analysis as the study proceeded. Overall, a total of 413 ultrasounds were performed in lupus patients and 325 in controls.

Remission was evaluated according to so-called DORIS (Definition of Remission in SLE) criteria. Targets for cardiovascular risk factors were based on standard recommendations, such as blood pressure below 140/90 mm Hg and body mass index of 25 or less. Others, like blood lipids, were individualized according to factors such as sex and overall cardiovascular risk score at baseline.

All participants were white, and more than 90% were women. Median blood pressure at baseline stood at 116/71 mm Hg for patients and 120/76 mm Hg among controls. Some 45% of patients and 31% of controls were current smokers, and slightly more patients had a family history of coronary artery disease (14% vs 12%). Median LDL cholesterol values were 108 and 121 mg/dL at baseline for patients and controls, respectively; median body mass index was 25 in patients and 24 in controls.

Besides the finding that successful risk-factor reduction and disease remission decreased atherosclerosis risk, the researchers also determined that positivity for three antiphospholipid antibody species (“triple aPL”) — IgG and IgM anticardiolipin and anti-β2 glycoprotein I antibodies along with lupus anticoagulant — throughout follow-up was significantly associated with risk for cardiovascular events (HR 7.52, 95% CI 1.51-37.5), compared with patients not sharing this characteristic. Persistent positivity for lupus anticoagulant appeared particularly important, with a hazard ratio of 12.99 (95% CI 3.07-55.0).

Tektonidou and colleagues noted that previous studies had tied positive results for aPL species to increased cardiovascular risk, but this is the first to focus specifically on triple positivity as a significant risk factor. The group cautioned, though, that aPL testing was not performed in controls.

Another potentially related finding was that among the eight lupus patients developing cardiovascular events, seven were predicted to be at low to moderate risk for such events according to both SCORE and SCORE2 risk calculators. Tektonidou and colleagues found, too, that a model that added the presence of atherosclerosis at baseline improved event prediction in their SLE patients. Including aPL positivity as well might make risk stratification even more accurate, the results suggested.

Clearly, the group wrote, “generic CVD prediction tools, such as Framingham and SCORE, may underestimate CVD risk in SLE.”

Limitations to the analysis included the small number of cardiovascular events observed during the study and the lack of racial-ethnic diversity among participants. Also, 20 controls quit the study or were lost to follow-up prior to year 10.