AS Linked to Impaired Small Blood Vessels, But Manageable with Certain Inhibitors

TNF-α inhibitors have the potential to prevent heart disease among patients with ankylosing spondylitis (AS) by improving blood flow in small blood vessels, researchers suggest.

Their study, “Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment,” was published in the journal Scientific Reports.

From 30% to 50% of patients with ankylosing spondylitis are at an increased risk of experiencing cardiovascular events compared to the general population.

Although it’s unclear why this happens, researchers believe that disease-associated inflammation and deregulation of cardiovascular risk factors are important contributors.

Studies suggest that AS is accompanied by alterations in the function of major blood vessels, which can directly support the underlying mechanisms of atherosclerosis, hypertension, and heart failure.

Now, researchers in Poland assessed whether the dysfunction of small blood vessels (microvasculature), which is often related to early heart problems, could also contribute to ankylosing spondylitis-associated cardiovascular risk.

The study enrolled 54 patients with confirmed AS, of whom 22 had high disease activity despite treatment with non-steroidal anti-inflammatory drugs (NSAIDs).

Patients had no history of corticosteroid or biological anti-inflammatory therapy. Twenty-eight age- and sex-matched healthy volunteers were also included as controls.

Blood flow in the small vessels (capillaries) beneath the skin was evaluated using a non-invasive technique called Laser Doppler Flowmetry (LDF). With this approach, researchers could assess several blood flow parameters and evaluate microvasculature function.

A first analysis revealed that, when compared to controls, ankylosing spondylitis patients needed double the time to deliver an appropriate blood supply to different organs and restore the normal balance in a skin area where the blood flow had been temporarily blocked.

This blood flow impairment was found to be due to the abnormal network of small blood vessels, including bushy and coiled vessels, branched capillaries, and swelling of the capillaries surrounding tissues.

To evaluate whether the observed differences were associated with disease activity, researchers divided patients into two groups based on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Basal blood flow was similar between patients with controlled and active disease (BASDAI greater than or equal to 4). But patients with active disease had a significantly slower blood flow response in the test.

Of note, basal blood flow refers to how fast or slow an individual’s blood flow runs within their body.

Patients with active disease were then treated with TNF-α inhibitor compounds for three months. Thirteen patients were treated with Humira (adalimumab), six with Enbrel (etanercept), and three patients received Remsima (infliximab).

These treatments significantly helped manage disease symptoms, resulting in a reduction of disease activity and pain scores.

When researchers repeated blood flow evaluations after three months of anti-TNF-α treatments, they found significant improvements in all microcirculation parameters analyzed. Specifically, basal blood flow was increased and time of response for restoring blood flow was reduced.

But these improvements were not found to be related to changes in microvasculature network structures. Indeed, blood vessels looked similar to the way they were before the treatment, with no changes in the type of visible capillaries, density, and distribution. Only the swelling of surrounding tissues was decreased, which could have contributed to an improved blood flow.

Collectively, these findings demonstrate that “microvascular impairment in ankylosing spondylitis is associated with disease activity,” which could help “explain the increased cardiovascular risk seen in this chronic condition,” researchers wrote.

“TNF-α inhibitors may be effective not only in improving the signs and symptoms of [ankylosing spondylitis] but also in preventing cardiovascular complications,” they added.

Additional studies are necessary to better understand the impact of different types of TNF-α inhibitors and what type of changes they can potentially promote in microcirculation.

“This could be essential in the treatment choice for patients with high cardiovascular risk and such large randomized studies will hopefully clarify this in the future,” they concluded.