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Vascular endothelial injury assessed with functional techniques in systemic sclerosis patients with pulmonary arterial hypertension versus systemic sclerosis patients without pulmonary arterial hypertension: a systematic review and meta-analysis

Microvascular dysfunction is one of the hallmarks of systemic sclerosis (SSc). The presence of pulmonary-arterial-hypertension (PAH) in SSc-patients is associated with poor prognosis. This is a systematic review and meta-analysis of studies assessing microvascular and endothelial injury with functio...

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Published in:Rheumatology international 2021-06, Vol.41 (6), p.1045-1053
Main Authors: Theodorakopoulou, Marieta P., Minopoulou, Ioanna, Sarafidis, Pantelis, Kamperidis, Vassilios, Papadopoulos, Christodoulos, Dimitroulas, Theodoros, Boutou, Afroditi K.
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Language:English
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Summary:Microvascular dysfunction is one of the hallmarks of systemic sclerosis (SSc). The presence of pulmonary-arterial-hypertension (PAH) in SSc-patients is associated with poor prognosis. This is a systematic review and meta-analysis of studies assessing microvascular and endothelial injury with functional techniques in SSc-patients with PAH (SSc–PAH) compared to those without PAH (SSc–non-PAH) (PROSPERO: CRD42021236212). Literature search involved PubMed, the-Cochrane-Library, Web-of-Science, Scopus and manual search of article references. Studies assessing microvascular function by all available functional methods were considered eligible. Preclinical studies and studies using structural nailfold-videocapillaroscopy or biomarkers were excluded. Newcastle–Ottawa-Scale (NOS) was applied to evaluate the quality of retrieved studies. From a total of 602 retrieved articles, four studies ( n  = 159 participants) were included in meta-analysis; three studies were of high quality (NOS ≥ 7). In pooled analysis, a marginally significant impaired microvascular function was observed in SSc–PAH compared to SSc–non-PAH patients [SMD − 0.71, 95% CI (− 1.53, 0.12)], with significant between-study heterogeneity ( I 2  = 80%, p  = 0.002). Among the studies examining endothelium-dependent and -independent vasodilation with LDF-iontophoresis, SSc–PAH subjects had significantly impaired endothelium-dependent-vasodilation [Ach-stimulated %change WMD − 216.79, 95% CI (− 337.87, − 95.71), I 2  = 0%, p  = 0.40], but no significant differences in endothelium-independent-vasodilation [SNP-stimulated %change WMD 90.84, 95% CI (− 82.52, 264.19), I 2  = 44%, p  = 0.18] compared with SSc–non-PAH subjects. In sensitivity analysis including only studies where SSc–PAH patients were diagnosed by right-heart-catheterization, a borderline difference between the two groups was noted [SMD − 1.09, 95% CI (− 2.30, 0.13), I 2  = 82%, p  = 0.004]. SSc–PAH patients showed marginally impaired microvascular function in the pooled analysis, as well as impaired endothelium-dependent-vasodilation in subgroup analysis compared with SSc–non-PAH patients. Vascular endothelial dysfunction could be involved in high cardiovascular risk of patients with SSc and PAH.
ISSN:0172-8172
1437-160X
DOI:10.1007/s00296-021-04850-2