Risk of Aorta Damage With Vascular EDS May Be Due Mostly to Aging
Study suggests aortic lesions depend more on age than COL3A1 mutation type
As people with vascular Ehlers-Danlos syndrome (vEDS) age, their risk of damage to the aorta, a large artery carrying blood from the heart to the body, rises, a study suggests.
The study, “Assessment of arterial damage in vascular Ehlers-Danlos syndrome: A retrospective multicentric cohort,” was published in the journal Frontiers in Cardiovascular Medicine.
Vascular EDS is mainly caused by mutations in the COL3A1Â gene, which provides instructions for making part of a structural protein called type III collagen. Impairment in this protein’s function leads to disease symptoms that include fragile blood vessels and a high bleeding risk.
Study finds risk in ‘vascular aging on already fragile arteries’
Mutations in COL3A1 can be divided into two broad types. Dominant-negative (DN) mutations result in the production of a protein that interferes with the activity of other, healthy proteins, and these mutations are usually associated with a more severe course that causes problems earlier in life. Haploinsufficiency (HI) mutations, which refer to a single functioning copy of a gene not being enough for normal function, tend to result in disease that manifests later in life.
Usually, the blood vessels most affected in vEDS are medium-size arteries. The aorta, one of the largest blood vessels, is the main artery that carries oxygen-rich blood from the heart out toward the rest of the body. Although it’s not as common for the aorta to be affected in vEDS, patients with the disease can develop aortic lesions.
Recent reports suggest that aortic lesions are more common in vEDS caused by HI mutations than DN mutations. However, since people with either of these two mutation types tend to be different ages when they start experiencing problems, it hasn’t been clear whether this difference is due to the underlying mutation, or due to differences in how the vascular system changes as a person ages.
A team led by scientists in France and Canada conducted a study to learn more.
“Our goal was to investigate possible differences in MSA [medium-size arteries] and aortic involvement between the two main types of COL3A1 variants (DN vs. HI) and their possible dependency on normal vascular aging,” the researchers wrote.
Their analysis included data on 330 adults with vEDS. Among these patients, 80.6% had a DN mutation, while the other 19.4% had a HI mutation. Patients with DN mutations tended to be younger (average of 33 years old) than those with HI mutations (average of 46) when they first experienced a disease-related arterial event. But the researchers noted that, despite the earlier age at onset with DN, age at disease diagnosis was comparable for both mutation types in patients with the same arterial presentation.
“As expected from previous publications, patients with DN had their first arterial event at a younger age than HI patients, but this finding did not seem to influence the time to vEDS molecular diagnosis in either group,” the researchers wrote.
The majority (82.4%) of the patients had some form of arterial lesions, or damage to their medium-size arteries and/or the aorta. Among this group, 83.5% had MSA lesions only, 3.3% had aorta lesions only, and 13.2% had both MSA and aorta lesions.
A significantly greater proportion of patients with DN mutations had some form of arterial lesion compared with those with HI mutations (84.6% vs. 73.4%). The researchers noted that rates of MSA events in the kidneys and neck were especially common among people with DN mutations, which “is an argument for more aggressive care and cardiovascular prevention in these particularly vulnerable patients.”
In line with earlier reports, the overall prevalence of aorta lesions was higher among vEDS patients with HI mutations than DN mutations (28% vs. 14%). However, when the researchers made statistical adjustments to account for differences in age, the rate of aorta lesions was similar in both groups.
“The difference disappeared after age adjustment, and aortic lesion occurrence seems dependent on age in both COL3A1 variants (DN and HI),” the researchers wrote. Both mutation types also showed similarities in age-adjusted measures of arterial stiffness.
“Vascular aging on already fragile arteries might thus explain the age-dependent high frequency of aortic lesions in vEDS. Therefore … patients with vEDS should be considered at risk for aortic events when getting older, regardless of their genotype,” the researchers concluded.
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