Review Article | Published:

Microvascular endothelial dysfunction in rheumatoid arthritis

Nature Reviews Rheumatologyvolume 14pages404420 (2018) | Download Citation


The systemic autoimmune disease rheumatoid arthritis (RA) is characterized by increased cardiovascular mortality and morbidity and is an independent cardiovascular risk factor. Cardiovascular diseases (CVDs) result from accelerated atherogenesis, which is a consequence of endothelial dysfunction in the early stages of the disease. Endothelial dysfunction is a functional and reversible alteration of endothelial cells and leads to a shift in the properties of the endothelium towards reduced vasodilation, a pro-inflammatory state, and proliferative and prothrombotic properties. In RA, endothelial dysfunction can occur in the large vessels (such as the conduit arteries) and in the small vessels of the microvasculature, which supply oxygen and nutrients to the tissue and control inflammation, repair and fluid exchange with the surrounding tissues. Growing evidence suggests that microvascular endothelial dysfunction contributes to CVD development, as it precedes and predicts the development of conduit artery atherosclerosis and associated risk factors. As such, numerous studies have investigated microvascular endothelial dysfunction in RA, including its link with disease activity, disease duration and inflammation, the effect of treatments on endothelial function, and possible circulating biomarkers of microvascular endothelial dysfunction. Such findings could have important implications in the cardiovascular risk management of patients with RA.

Key points

  • Microvascular endothelial dysfunction is an early and/or seminal event in the development of cardiovascular diseases and associated organ damage and is also present in patients with rheumatoid arthritis (RA).

  • Microvascular endothelial dysfunction does not correlate with disease activity, disease duration, levels of C-reactive protein or the erythrocyte sedimentation rate.

  • Antirheumatic drugs and other therapies can be used to treat microvascular endothelial dysfunction, but the effects of these therapies differ.

  • Achieving remission in RA does not guarantee the normalization of microvascular endothelial function.

  • Semiautomated methods for the measurement of microvascular endothelial dysfunction exist; therefore, the concept of endothelial-guided therapies in RA deserves attention.

  • The predictive value of microvascular endothelial dysfunction for cardiovascular events needs to be demonstrated in future studies.

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  1. PEPITE EA4267, FHU INCREASE, Universitaire Bourgogne Franche-Comté, UFR Santé, F-25000, Besançon, France

    • Romain Bordy
    • , Perle Totoson
    • , Clément Prati
    •  & Céline Demougeot
  2. Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de Besançon, F-25000, Besançon, France

    • Clément Prati
    •  & Daniel Wendling
  3. INSERM UMR1093 CAPS, Universitaire Bourgogne Franche-Comté, UFR des Sciences de Santé, F-21000, Dijon, France

    • Christine Marie
  4. EA 4266, Universitaire Bourgogne Franche-Comté, UFR Santé, F-25000, Besançon, France

    • Daniel Wendling


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C.D. and R.B. researched data for the article and wrote the article. C.D. provided substantial contribution to the discussion of its content. All authors reviewed and/or edited the article before submission.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Céline Demougeot.

Supplementary information



A disorder of lipoprotein metabolism characterized by a spectrum of quantitative and qualitative changes in lipids and lipoproteins.

Framingham risk score

An algorithm used to estimate the 10-year risk of developing coronary heart disease on the basis of age, sex, cholesterol levels, blood pressure (and whether the individual is being treated for hypertension), diabetes and smoking status.

Pulsatile pressure

The difference between the systolic and diastolic blood pressure (also called pulse pressure), which is governed by the relationship between ventricular ejection and the viscoelastic properties of the large arteries (arterial stiffness).

Reactive hyperaemia

A transient increase in blood flow that occurs following a brief period of ischaemia (for example, arterial occlusion).

Myocardial ischaemia

A restriction in blood supply to the myocardium resulting from reduced blood flow in the coronary arteries. This restriction leads to an imbalance between myocardial oxygen supply and demand, causing cardiac dysfunction, myocardial infarction, arrhythmias and sudden death.

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