Jason C. Kovacic, MD, PhD; back row center, and Jeffrey W. Olin, DO, second from right; with team members, from left, Daniella Kadian-Dodov, MD; Annette King, NP; Bhargavi Vonguru, MSc; and Valentina d’Escamard, PhD.
A Mount Sinai team has gained valuable insights into fibromuscular dysplasia (FMD), a disorder of the arteries that is typically diagnosed in otherwise healthy women at midlife and sometimes causes aneurysms or serious heart disease. The findings could open the door to new strategies for the diagnosis, treatment, and management of FMD, including a blood test that could lead to earlier diagnosis.
“A lot of work remains, but we have proved that a reliable, blood-based test for this disease is eminently possible,” says Jason C. Kovacic, MD, PhD, Professor of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, and corresponding author of a study published in August 2019 in Cardiovascular Research. “Such a test could have an enormous impact on the management of FMD. It could pave the way for screening and counseling of family members, and for tailoring clinical care to patients who, in many cases, remain undiagnosed until they suffer a major event.”
The team compared blood samples from 90 women with FMD and 100 women without it, evaluating nearly 1,000 proteins and 31 lipid subclasses. Eventually, researchers identified and validated 37 proteins and 10 lipid sub-classes that make up a unique FMD disease signature. Then, machine learning was used to develop a prototype blood test for FMD.
Fibromuscular dysplasia (FMD) can affect arteries throughout the body. Arteries to the kidney of a patient with FMD, left, have a “string of beads” appearance, compared with normal arteries, right. A team at Mount Sinai is in the early stages of developing a blood test for the disease, which can cause aneurysms, heart attacks, or stroke.
“This is preliminary, but it is the first meaningful, mechanistic research that has been done in this disease,” says Jeffrey W. Olin, DO, Professor of Medicine (Cardiology), Icahn School of Medicine, and a co-author of the study. Developing an accurate test is crucial, says Dr. Olin, a leader in the treatment of FMD. “It’s not uncommon for a patient to have high blood pressure related to FMD that started when she was 30, and not have FMD diagnosed until she is 50,” he says.
FMD is a genetic disease that predominantly affects women and can strike at any age, although the average age of patients at diagnosis is 52. Abnormal cells form in the arteries, which take on a characteristic “string of beads” appearance, causing narrowing, tearing, or bulging of the vessels.
“FMD can affect the arteries of the kidney, causing high blood pressure. It can affect the arteries to the brain, which can cause stroke, or it can affect the arteries in the heart, in which you can develop a heart attack,” Dr. Olin explains. The prevalence of the disease is hard to gauge, because most patients with FMD have no symptoms for many years, and it is often found in a scan for another clinical purpose. For example, “FMD is discovered in approximately 4 percent of potential kidney donors, but this may be a serious underestimation of its prevalence,” he says.
Mount Sinai is in the forefront of efforts to unravel the genetics of FMD, due to the work of Dr. Kovacic and Dr. Olin, who is principal investigator for the United States Registry for Fibromuscular Dysplasia, and Director of the Mount Sinai Heart Center for Fibromuscular Dysplasia Care and Research. The team also includes Daniella Kadian-Dodov, MD, Assistant Professor of Medicine (Cardiology); Valentina d’Escamard, PhD, a senior scientist in the Kovacic Lab; and Annette King, NP, study coordinator.
“We are looking for a genetic profile of this disease, and we do have some promising preliminary results,” Dr. Olin says. “But ultimately, we want to find the gene or genes that cause this disease, and develop a treatment that blocks the effects of those genes.”