Severe SLE flares linked to high risk of stroke, 16 years of data show
Increased risk for younger patients found in new population study
Severe flare-ups of systemic lupus erythematosus (SLE) among patients were associated with a markedly higher risk of stroke, according to the results of a population-based study in Taiwan that analyzed data spanning 16 years.
Importantly, an overall elevated stroke risk was seen for younger adults with SLE who had few additional risk factors related to stroke.
Maintaining low lupus activity, both in the early and late stages of the disease, is essential to prevent stroke, the researchers concluded.
“Compared to SLE patients without severe lupus flare-up, the risk of … stroke increased dramatically among those who had experienced severe” flares of the chronic autoimmune disorder, the team wrote.
The population-based study, “Severe lupus flare is associated with a much higher risk of stroke among patients with SLE,” was published in the International Journal of Stroke.
Long-term study in Taiwan focuses on risk of stroke in SLE
SLE, the most common form of lupus, is a chronic disease driven by the immune system’s misdirected attack against healthy tissues. This causes widespread inflammation and tissue damage in affected tissues and organs, including the joints, skin, brain, lungs, kidneys, and blood vessels.
In some cases, patients can experience disease flare-ups, which refer to episodes of marked symptom worsening in one or more organs. Such flares can lead to clinical deterioration, new organ involvement, or worsening lab tests. Severe flares can increase the risk of hospitalization, permanent organ damage, and death.
Previous studies have found that people with SLE have a higher risk of stroke, which can happen when blood supply to a part of the the brain is reduced or interrupted. This can be due to a blood clot, in which case it’s called ischemic stroke, or occur when a blood vessel ruptures, causing bleeding in the brain — a hemorrhagic stroke.
To date, however, the risk of stroke in SLE adults experiencing severe lupus flare-ups has not been explored.
Using Taiwan’s National Health Insurance (NHI) Research Database, a team of scientists now sought to learn more. The team conducted a large-scale population-based study to investigate the relationship between flare-ups and stroke risk in adults with SLE.
“To the best of our knowledge, this study is the first to focus primarily on assessing the risk of stroke in SLE patients experiencing severe lupus flare,” the researchers wrote.
Medical records were examined from 10,006 patients diagnosed with SLE, of whom 88.5% were female. Among them, 334 experienced a severe flare, defined as a significant increase in SLE activity requiring high doses of in-hospital into-the-vein (intravenous) methylprednisolone pulse therapy.
Overall, the patients experiencing severe flare-ups were younger and had fewer established cardiovascular risk factors compared with the remaining 9,672 SLE patients who were assigned to the non-severe flare group. Controls included 10,006 age- and sex-matched individuals without SLE.
All participants were followed until a stroke or death, removal from the NHI database, or the end of the 16-year follow-up, whichever occurred first.
Ischemic stroke occurred in 8.7% of SLE patients (29 in all) with severe flares, compared with 5% (485 individuals) in the non-severe flare group and 3.8% of controls (384 people). Hemorrhagic stroke occurred in 2.7% or nine of the severe flare-up SLE patients. That proportion was 1.3% of non-severe flare patients (123 individuals), and 0.4% of controls (37 people).
Statistical analyses showed the overall risk of stroke was more than eightfold higher (8.18 times) in SLE patients with severe flares and 1.67 times higher in non-severe flare patients compared with controls.
The risk of ischemic stroke was more than sevenfold higher (7.44 times) in patients with severe flares and 1.52 times higher in those without severe flares compared with controls. A greater risk of hemorrhagic stroke — 22.49 times higher in the severe flare-up group and 4.47 times higher in the non-severe flare group — also was seen, as compared with controls.
Compared with the non-severe flare-up group, patients with severe flare-ups had a progressively higher incidence of ischemic stroke over a 10-year period following SLE diagnosis. From the fifth year after diagnosis, there was a second abrupt acceleration in ischemic stroke risk among SLE patients, including those with and without severe flare-ups.
For the patients who have been diagnosed with SLE for several years, sustained low disease activity is essential in long-term SLE management to prevent [stroke due to a blood clot].
Statistical survival analyses showed the probability of stroke-free survival — including that of overall, ischemic, and hemorrhagic strokes — was lower in patients with severe flare-ups compared with those without flares and controls.
The team suggested that lupus-related blood clot formation and other delayed-onset disease processes might have contributed to the increased risk of stroke in this study population.
“Our results support the importance of controlling lupus activity to lessen the risk of stroke in the early years after SLE diagnosis,” the researchers wrote. “For the patients who have been diagnosed with SLE for several years, sustained low disease activity is essential in long-term SLE management to prevent ischemic stroke.”