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

Bogdan Batko,Natalia Ryszawa-Mrozek,Marta Czesnikiewicz-Guzik,Eilidh Mcginnigle,Pawel Maga,Mateusz Koziej,Tomasz J Guzik,Tomasz Mikolajczyk,Karol Urbanski,Piotr Ceranowicz,Agata Schramm-Luc

doi:10.1038/s41598-018-31550-y

Bogdan Batko, Natalia Ryszawa-Mrozek + Show 9 more

Open Access

https://doi.org/10.1038/s41598-018-31550-y

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Journal: Scientific Reports	Publication Date: Sep 4, 2018
Citations: 18	License type: open-access

Affiliation: Jagiellonian University, University of Glasgow

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.

Highlights

Ankylosing spondylitis (AS) is associated with elevated cardiovascular (CV) risk and increased mortality[1,2,3,4], as an independent CVD risk factor
Microcirculation parameters studied using Laser Doppler Flowmetry (LDF) with Post-Occlusive Reactive Hyperemia (PORH) were impaired in AS patients compared to healthy controls
AS was associated with an abnormal microvascular morphology, with increased occurrence of loops enlargements, bushy and coiled, and branched capillaries as well as pericapillary edema compared to healthy controls (20.4% vs 3.6%, p = 0.04; 75.9% vs. 21.4%, p < 0.001; 37% vs. 14.3%, p = 0.03; 46.3% vs. 3.6%, p < 0.001 respectively) (Table 3)

Summary

Introduction

Ankylosing spondylitis (AS) is associated with elevated cardiovascular (CV) risk and increased mortality[1,2,3,4], as an independent CVD risk factor. Remains unclear whether this relationship is caused by prevalence of classical CVD risk factors or is linked to AS specific inflammatory factors It is unclear how such dysfunction is linked to AS disease activity. Using physiological stimulus – hyperemia and Laser Doppler Flowmetry (LDF), in a well powered analysis, we have confirmed presence of microvascular dysfunction in a low classical CVD risk population, and observed a clear relationship between functional microvascular impairment, morphological changes and AS activity. We demonstrated that functional impairment and capillary edema can be reversed by anti-TNF treatment, suggesting a key role of this drug therapy in microvascular dysfunction in patients with highly active AS. Simple tools for the measurement of microvascular function in the skin, available in typical outpatient setting, may give a valuable insight into microvascular function and structure and can be monitored in relation to its effects on cardiovascular risk

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