MIAMI BEACH – The mystery shrouding fibromuscular dysplasia, a clinically important and surprisingly prevalent vascular disease of unknown etiology, began to lift with initial findings from 339 patients enrolled in the first U.S. registry for the disease.
Baseline observations from the U.S. Registry for Fibromuscular Dysplasia (FMD), which enrolled its first patient in 2008 and currently has women as 91% of enrolled patients, show that the disease first occurs across a broad swath of age groups, with an age at first diagnosis ranging from 5 to 83 years old. In addition to the distinctive "string of beads" arterial fibrosis appearance that defines the disease and is apparent on imaging, and which usually occurs in the renal or carotid artery, or both, 19% of patients also had a dissection in an artery somewhere in their body (14% with a dissection in a carotid artery) and 17% had an arterial aneurysm somewhere (5% with a renal artery aneurysm and 4% with a carotid aneurysm).
"A patient can have normal blood pressure and normal-appearing carotid and renal arteries but have terrible headaches and FMD. Why? We don’t know."
These dissection and aneurysm prevalence rates had not previously been appreciated to run so high in FMD patients. "It suggests a diffuse arteriopathy that can present in several different ways," Dr. Jeffrey W. Olin said at ISET 2012, an international symposium on endovascular therapy.
Another notable finding was that, besides hypertension, which was the most common presenting manifestation of FMD (seen in 66% of the registry patients at initial diagnosis), other common presenting symptoms included significant, often migraine-like headache in 53%, pulsatile tinnitus (a whooshing sound patients hear) in 30%, and dizziness in 28%. The high prevalence of headache in FMD had been "first reported 30 years ago, but sort of got lost," Dr. Olin said in an interview.
"A patient can have normal blood pressure and normal-appearing carotid and renal arteries but have terrible headaches and FMD. Why? We don’t know. We have no idea what causes the headaches," said Dr. Olin, a cardiologist who is professor of medicine and director of vascular medicine at Mount Sinai Medical Center in New York. Four percent of the registry patients had no symptoms on presentation; physicians found their FMD incidentally during imaging examinations for other reasons.
Other flags to trigger suspicion of FMD include hypertension that begins before age 35 (although it can also start later in life), treatment-resistant hypertension, epigastric bruit and hypertension, renal infarction, cervical bruit in a patient less than 60 years old, transient ischemic attack or stroke in a patient less than 60 years old, or an aortic aneurysm in a patient less than 60 years old.
Perhaps the most surprising new finding so far from the registry is evidence for a strong family history of cardiovascular disease, with 81% of first- or second-degree relatives of FMD patients having hypertension, 59% with hyperlipidemia, 53% with a history of a stroke, 22% with an aneurysm, and 21% with a history of sudden death. The prevalence of a first- or second-degree relative also having a diagnosis of FMD was 7%, not much higher than the currently estimated 4% prevalence of FMD in the general population.
Dr. Olin and his associates from the registry hypothesize that patients who develop FMD have an as-yet unidentified genetic predisposition that interacts with an environmental trigger. His hope is that, by continuing to expand the registry and by receiving substantially more research support than FMD now gets, a more concerted research effort can address the genetic questions raised by the family-history findings.
Current treatment of FMD is symptom driven and usually focuses on trying to resolve patients’ hypertension, which is often treatment resistant.
"FMD is potentially treatable for hypertension," with endovascular treatment of affected renal arteries the standard intervention for patients with resistant hypertension, Dr. Robert A. Lookstein said in a separate talk at the meeting. Hypertension cure rates from balloon angioplasty, however, are "surprisingly low" – 45% in one meta-analysis – probably because of suboptimal interventional treatment, said Dr. Lookstein, chief of the division of interventional radiology at Mount Sinai.
Assessing a patient’s renal arteries before and during treatment using intravascular ultrasound (IVUS) and a pressure wire provides the key to successful resolution of hypertension by renal-artery angioplasty in FMD patients, he said.
These two techniques, especially pressure-wire measurements, allow the operator to assess the patient’s renal arteries before and during treatment to determine whether the intervention is having a meaningful effect. "You can’t tell [whether the angioplasty produced benefit] by the angiography appearance alone," he cautioned. "You need to be compulsive with IVUS and measuring pressure gradients to determine where to start treatment and when to stop."