Revisiting Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) has been defined as an idiopathic, segmental, nonatherosclerotic, and noninflammatory disease of the musculature of arterial walls, leading to stenosis of smalland medium-sized arteries. Furthermore, to confirm the diagnosis of FMD, arterial diseases of monogenic origin, inflammatory arterial diseases, and the use of arterial vasoconstrictors have to be excluded. Renal FMD may lead to renovascular hypertension, less frequently renal artery dissection, renal infarction, and aneurysm rupture. Cervico-cephalic FMD can result in ischemic or hemorrhagic stroke, cervical artery dissection, and may be also associated with intracerebral aneurysms and risk of subarachnoid hemorrhage. In some patients, the diagnosis of FMD can lead to invasive procedures, such as percutaneous angioplasty, reconstructive surgery, or intracranial aneurysm clipping. Thus, both the disease and its treatment can lead to significant morbidity and mortality. The French and the US registries have led to a reappraisal of the frequency, demographic characteristics, classification, pathophysiology, and management of FMD. The face of the disease is evolving from a rare disease of renal arteries accounting for a minority of cases of secondary hypertension in young women to a "systemic" vascular disease affecting renal and also cervico-cephalic, coronary, and iliac arteries (Table 1). In various cohorts, despite incomplete exploration, mostly driven by symptoms and clinical complaints, FMD of ≥2 vascular beds was consistently found in >30% of cases. The French ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry, which required a standardized vascular work-up in all patients, will soon provide a more precise estimate of the frequency of diffuse FMD. Besides female sex and repeated mechanical trauma because of increased kidney mobility, recent works suggest a contribution of smoking in progression of the disease, as well as a genetic susceptibility. High-resolution cardiac echo-tracking, mechanistic, biochemical, and genetic studies will soon lead to a better understanding and classification of the disease. Furthermore, registries should help to identify characteristics of patients likely to develop extensive, progressive, or complicated forms of FMD. Progresses in the understanding of the disease and research perspectives have been extensively reviewed on the occasion of the First National Meeting on Fibromuscular Dysplasia, endorsed by the European Society of Hypertension, which took place in Brussels on December 12, 2015, (http://www. saintluc.be/professionnels/agenda/2015/2015-12-12-fibromuscular-dysplasia.pdf), and summarized for an expert audience on the occasion of the 10th International Workshop on Structure and Function of the Vascular System (Paris, February 4–6, 2016). This short review covers the highlights of these meetings and provides the rationale for the European FMD initiative (see list of centers currently involved in the online-only Data Supplement).