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.

Potential Role and Impact of Peripheral Blood Mononuclear Cells in Radiographic Axial Spondyloarthritis-Associated Endothelial Dysfunction

“…Over the last few years, several research groups have demonstrated that systemic inflammation plays a crucial role in promoting ED and accelerated atherosclerosis [10], thereby supporting the idea that chronic systemic inflammation may be a main contributor to the development of a dysfunctional endothelium in r-axSpA. In our study, we found that plasma inflammatory status was associated with endothelial function, a fact previously observed by van Eijk et al [14] and Batko et al [15], who showed that disease activity was related to microvascular dysfunction and that a reduction in inflammation with TNF-α blockade improved ED in r-axSpA patients. Notwithstanding, the cell determinants of such r-axSpA-associated endothelial abnormalities are unknown.…”

“…A variety of studies have shown that ED is a vascular abnormality frequently presented in r-axSpA patients [13][14][15], and peripheral blood mononuclear cells (PBMCs) might play a key role in its triggering, initiation, and development. In r-axSpA, T lymphocytes, a cell subtype crucial in the immune system regulation [16], have been demonstrated to be central elements in the pathology [17].…”

The pathogenic role of coronary microvascular dysfunction in the setting of other cardiac or systemic conditions

“… 89 Several studies have also shown systemic microvascular dysfunction as measured in peripheral vascular beds in patients with RA and AS. 72 , 90 Interesting insight into the CMD can be gained from the analysis of skin microvasculature, which has been shown to offer a useful model to study arteriole function and capillary morphology. 91 Findings from these studies are in line with earlier invasive observations that NO-mediated, acetylcholine-induced vasorelaxation in microvessels is impaired in AS and may improve with anti‐TNF-α therapy.…”

“… 91 Findings from these studies are in line with earlier invasive observations that NO-mediated, acetylcholine-induced vasorelaxation in microvessels is impaired in AS and may improve with anti‐TNF-α therapy. 86 , 90 In similarity to large vessel endothelial dysfunction, microvascular dysfunction has been identified in a number of inflammatory conditions, such as severe chronic periodontitis, 92 or inflammatory bowel disease, 93 where impairment correlates with CRP. Thus, inflammation may provide a mechanistic link between these comorbidities and cardiovascular events.…”

“…In fact, other studies have shown that clinical inflammatory burden in patients with AS is associated with microvascular flow impairment. 72 Notably, some interventional evidence shows that anti-inflammatory biological therapies such as anti-TNF treatments lead to improvement of coronary and peripheral microvascular dysfunction, 90 although results are often conflicting and not emerging from randomized or placebo-controlled studies. 72 …”