Microvascular dysfunction in ankylosing spondylitis is associated with disease activity and is improved by anti-TNF treatment

Abstract

Ankylosing spondylitis (AS) is associated with high cardiovascular morbidity and mortality. Recent studies indicate that microvascular dysfunction may underlie cardiovascular risk in AS. We hypothesized, that microvascular morphology and dysfunction is linked to AS activity and is modifiable by TNF-α inhibitor (TNFi) treatment. Functional Laser Doppler Flowmetry with post-occlusive reactive hyperemia, and structural nailfold capillaroscopy were performed in 54 patients with AS and 28 matched controls. Active AS was diagnosed based on BASDAI ≥ 4 (n = 37). Effects of 3-month TNFi on microcirculation in active AS were studied. AS was associated with prolonged time to peak hyperemia compared to healthy controls. High disease activity was associated with increased time to peak hyperemia and decreased peak hyperemia when compared to patients with inactive AS. In capillaroscopy, AS was associated with morphological abnormalities indicating increased neoangiogenesis and pericapillary edema compared to controls. Microvascular function improved following 3 months of TNFi in reference to basal flow as well as post-occlusive parameters. TNFi reduced pericapillary edema, while other parameters of capillary morphology remained unchanged. Microvascular dysfunction and capillary neovascular formation are associated with disease activity of AS. Anti-TNF-α treatment may restore microcirculation function and capillary edema but does not modify microvascular structural parameters.

Figure 1

Disease activity and microvascular function. Basal flow (a), peak hyperemia (b) and time to peak hyperemia (c) were measured in patients with active (n = 37) and inactive (n = 17) disease based on BASDAI score. Mann-Whitney U test was used. Data are expressed as median, interquartile range (box), 10–90 percentile (whiskers).

Figure 2

TNF-α inhibitor treatment and microvascular function. Basal flow (a), peak hyperemia (b) and time to peak hyperemia (c) were measured in patients before and 3 months after TNFi treatment (n = 22). (d) Sample test result of LDF and PORH: (left) patient before TNFi treatment, (right) after TNFi treatment: A - basal flow, B - PORH test – peak hyperemia after 5-minute occlusion. Wilcoxon signed-rank test was used. Data are expressed as median, interquartile range (box), 10–90 percentile (whiskers). TNFi – TNF-α inhibitor, LDF – Laser Doppler Flowmetry, PORH – Post-occlusive Reactive Hyperemia.