Rheumatology International

, Volume 38, Issue 7, pp 1179–1190 | Cite as

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

  • Gian Luca ErreEmail author
  • Giorgio Buscetta
  • Panagiotis Paliogiannis
  • Arduino Aleksander Mangoni
  • Ciriaco Carru
  • Giuseppe Passiu
  • Angelo Zinellu
Systematic Review


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.


Coronary flow reserve Atherosclerosis Rheumatic diseases Connective tissue diseases Rheumatoid arthritis Behcet’s disease 





Ankylosing spondylitis


Behcet’s disease


Body mass index


Cardiac magnetic resonance


95% Confidence intervals


Coronary flow reserve


C-reactive protein


Connective tissue diseases


Diastolic blood pressure




Erythrocyte sedimentation rate


High-density lipoprotein


Heart rate


Major histocompatibility complex


Low-density lipoprotein


Positron emission tomography


Rheumatic diseases


Rheumatoid arthritis


Systolic blood pressure


Systemic sclerosis


Standardized mean differences


Trans-thoracic stress echocardiography


Author contributions

GLE and AZ designed the study. GLE and AZ searched databases and performed the selection of studies; GLE, AZ, and AAM wrote the manuscript; PP and AZ analyzed the data; GB, CC, and GP contributed to writing and critically uprising the manuscript and approved the last version.


No grant support was utilized for this study.

Compliance with ethical standards

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.UOC Reumatologia, Dipartimento di Medicina Clinica e SperimentaleAzienda Ospedaliero-Universitaria di Sassari e Università di SassariSassariItaly
  2. 2.Dipartimento di Scienze BiomedicheUniversità degli Studi di SassariSassariItaly
  3. 3.Department of Clinical Pharmacology, College of Medicine and Public HealthFlinders University and Flinders Medical CentreAdelaideAustralia

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