Updated: Dec 30, 2021
Recent vascular EDS literature estimated the average life expectancy at 51 years(1). While innovative technologies like gene editing and CRISPR-Cas9 have us optimistic for a vEDS cure, they are still in their infancy. What can be done to extend life expectancy in vEDS now? Look no further than Marfan Syndrome, another connective tissue disorder like vEDS.
In 1972, the Marfan Syndrome average life expectancy was 48 years(2). Over the last three decades, Marfan Syndrome life expectancy has increased by 30 years(3)! With no breakthrough gene editing technology and no “wonder pill”, the Marfan Syndrome story provides a lesson for how vascular Ehlers-Danlos syndrome patients might see extended lives while researchers develop a cure…
Photo from Washington University School of Medicine in St. Louis Marfan Syndrome Clinic
Marfan Syndrome: A Related Condition to vEDS
Marfan Syndrome is a connective tissue disorder caused by issues in a protein called Fibrillin-1(4). Marfan Syndrome is similar to vEDS in the fact that some of its most severe symptoms are cardiovascular. The most commonly involved artery in Marfan Syndrome is the aorta. The aorta is the largest blood vessel in the body, responsible for carrying blood directly from the heart to other parts of the body.
In Marfan syndrome, the aorta can enlarge, which may lead to a bulge in the blood vessel wall called an aneurysm(4). Enlargement of the aorta can also lead to tearing of the layers in the aortic wall (aortic dissection). Aortic aneurysms and dissection can be life threatening(4).
A Dramatic Improvement in Marfan Syndrome Life Expectancy
From 1972 to 1995, Marfan Syndrome experienced a 24-year increase in average life expectancy:
1972: A research study documented a median probability of survival of 48 years of age, with most deaths being cardiovascular in nature(2). This study looked at patients retrospectively (data from patients in the past) who did not benefit from any effective medical or surgical treatment(3).
1972-1995: New medical and surgical techniques are introduced to treat Marfan Syndrome.
1995: An important paper is published in the American Journal of Cardiology which tried to determine if treatment (medical or surgical) had changed the prognosis and life expectancy in Marfan Syndrome(2). In the publication, the median age of survival in Marfan Syndrome had jumped to 72 years from the 48 years in the 1972 paper(2)!
What changed in Marfan Syndrome?
The American Journal of Cardiology article from 1995, and others published since, point to several advancements which may have led to the dramatic shift in survival(2,3):
Guidelines: Improved guidelines were created for when to repair aortic aneurysms. Repairing these aneurysms earlier, and before they became a bigger problem, improved outcomes. Nothing has had a greater impact on survival in Marfan Syndrome than effective, pre-emptive repair of enlarging aortic aneurysms(3).
Surgery: Surgeons adjusted and improved surgical techniques to repair aortic aneurysms. Standard practices for post-operative management were also adjusted, which reduced the number of complications from surgeries(3).
Medication and Medical Management:
Medications: The use of medications including particular beta-blockers and angiotensin receptor blockers has been shown to reduce stress on the aorta, slowing the rate of aortic dilation (enlargement) in Marfan Syndrome patients(3)
Surveillance: Regular monitoring of the aorta is now standard care in Marfan Syndrome. Physicians have worked to create more standardized criteria for when an aortic aneurysm should be operated on to improve outcomes(3)
Lifestyle adaptations: Marfan patients have been encouraged to avoid particular exercise activities which may be detrimental to their health(3). An example would be any activities that can cause chest trauma.
Improved Understanding of the Underlying Disease: Researchers made significant strides in understanding the underlying pathology (cause) of the disease. New molecules such as TGF-Beta were discovered. They are now thought to play a role in the disease and have prompted new research for potential treatments(3)
These advancements, plus other factors -- including an overall increase in average life expectancy of the general population and a larger number of milder Marfan syndrome cases being diagnosed -- have all contributed to the dramatic shift in outcomes in Marfan Syndrome(2,3).
What Can vEDS Learn from the Marfan Experience?
Marfan and vEDS are two different diseases. Marfan Syndrome is ahead of vascular EDS in an understanding of the disease, the underlying pathology that causes the disease and its symptoms, and the pursuit of medical treatments to target these issues. But there are important lessons to take away:
Improvements in Marfan Syndrome life expectancy were not driven by one groundbreaking new medication or cure
Incremental enhancements of guidelines, surgery, medication & medical management had major impacts on life expectancy in Marfan Syndrome
The good news for vascular EDS is that leading researchers are already working on many of the same things:
A Better Understanding: There are some amazing researchers working on vEDS to increase our understanding of the disease. One in particular is of interest for this blog—Dr. Hal Dietz. Dr. Hal Dietz is seen by many as the world expert in Marfan Syndrome. He has uncovered some of the biggest discoveries in Marfan Syndrome. Did you know that Dr. Dietz runs a lab at Johns Hopkins University dedicated to vascular EDS as well? His work is actively being supported by vEDS organizations like the DEFY Foundation. He, and many other bright minds, are hard at work trying to learn more about vEDS!
Medicine: In 2010, the BBEST Trial on celiprolol was published. It showed a reduction in the number of ‘adverse events’ such as arterial dissections and ruptures with the use of celiprolol vs. no treatment in patients with vascular EDS. There is still plenty of debate by US experts in vEDS as to whether celiprolol is the best medicine for vascular EDS patients or if other beta-blockers and ACE inhibitors are just as effective. But this trial suggests that there are medicines out there which can decrease the number of adverse events (arterial dissections, ruptures etc)—which in theory should/will lead to improvements in outcomes.
Guidelines: we do not currently have adequate guidelines for vascular EDS management. However, many researchers and patient advocacy groups recognize the need for improvements in this realm. Emergency Room protocols and other guidelines are high on the priority list and FIGHT vEDS will be working with these groups to get these to you as soon as possible.
At FIGHT vEDS we feel that there are lessons to be learned from Marfan Syndrome. Improved treatment guidelines, emergency protocols, and a clearer picture of when to intervene surgically are all realistic goals for the near future. There are some brilliant researchers working on vascular EDS who we are fortunate to have on our side. Let’s give them the time and support that they need to continue making progress. In the meantime, keep your head up, stay positive, and do your part to stay healthy!
Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin MG, Robert L, Sanders L, Wheeldon N. 2017. Diagnosis, natural history and management in vascular Ehlers-Danlos syndrome. American Journal of Medical Genetics Part C (Seminars in Medical Genetics). 175C:40-47.
Silverman DI, Gray J, Roman MJ, et al. Family history of severe cardiovascular disease in Marfan syndrome is associated with increased aortic diameter and decreased survival. J Am Coll Cardiol 1995;26:1062–7.
Pyeritz RE. Marfan syndrome: 30 years of research equals 30 years of additional life expectancy. Heart 2009; 95:173-175.