Coronary flow reserve in systemic rheumatic diseases: a systematic review and meta-analysis

Coronary flow reserve (CFR), a measure of both obstructive coronary artery disease and microvascular dysfunction, has been evaluated in systemic rheumatic diseases (RDs), but a comprehensive critical appraisal of the available evidence is lacking. The objective of this study is to conduct a systematic review and meta-analysis of studies with small sample size investigating the associations between the presence of RDs and CFR to increase statistical power and accuracy. PubMed, Web of Science, Scopus, and Google Scholar, from inception to March 2018, were searched for studies reporting on CFR in RDs in comparison to healthy subjects. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. Meta-regressions and sensitivity analyses assessed study heterogeneity by type of RDs, age, traditional cardiovascular risk factors, systemic inflammation, and methodology used to evaluate CFR. Twenty-one studies (709 RDs patients and 650 healthy controls) were included in the meta-analysis. Pooled results showed that CFR values were significantly lower in patients with RDs than in healthy controls (SMD = - 1.51, 95% CI - 1.91, - 1.11; p < 0.001; I² = 90.1%, p < 0.001). The between-group differences in CFR were not associated with inflammatory burden, age, lipids, body mass index, blood pressure, or assessment methods. Patients with prevalent autoimmune features (e.g., systemic lupus erythematosus) showed a significantly lower CFR when compared to patients with mixed autoimmune and autoinflammatory features (e.g., psoriatic arthritis). This meta-analysis showed a significant impairment in CFR in patients with RDs with respect to the general population. Differences in pathogenetic mechanisms may influence the severity of CFR impairment in RDs.