Abdominal aortic aneurysm: Genetic scoring can identify more men at risk

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May 07, 2020 – Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. AAAs usually cause no symptoms, except during rupture. Occasionally, abdominal, back, or leg pain may occur.  Rupture may result in pain in the abdomen or back, low blood pressure, or loss of consciousness, and often results in death. AAAs occur most commonly in those over 50 years old, in men, and among those with a family history. Additional risk factors include smoking, high blood pressure, and other heart or blood vessel diseases.  Genetic conditions with an increased risk include Marfan syndrome and Ehlers-Danlos syndrome. AAAs are the most common form of aortic aneurysm. About 85% occur below the kidneys with the rest either at the level of or above the kidneys. In the US screening with abdominal ultrasound is recommended for males between 65 and 75 years of age with a history of smoking. In the UK and Sweden, screening all men over 65 is recommended. Once an aneurysm is found, further ultrasounds are typically done on a regular basis. In other countries, aneurisms are mostly detected by chance in the course of consultations in connection with other diseases.

A very recent report in MedicalXPress indicates that a new genetic risk score based on 29 mutations in the blood identified more men at increased risk for an abdominal aortic aneurysm and who could benefit from screening to detect it prior to rupture, according to preliminary research presented at the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2020. The meeting is a virtual event in 2020, to be held May 5-7, and is a premier global exchange of the latest advances in new and emerging scientific research in arteriosclerosis, thrombosis, vascular biology, peripheral vascular disease, vascular surgery and functional genomics.might

Clinically, AAA occurs when there is enlargement or a weakening of the wall of the large blood vessel that supplies blood to the abdomen and lower body. If the aneurysm weakens the vessel wall to the point that it ruptures, it is a life-threatening medical emergency with a survival rate of about 20%. In order to detect more abdominal aortic aneurysms before it is an emergency, in December 2019, the United States Preventive Services Task Force (USPSTF) announced updated recommendations for a one-time ultrasound screening of men between 65 and 75 years of age who have ever smoked. If an aneurysm is detected, it can be monitored to determine if it is small, can be surgically repaired and allow for treatment if it grows large enough to raise concerns about rupture (more than 5.5 cm or 2-1/6 inches).

According to the current report, researchers  focused on whether they could use a series of genetic mutations to develop a score that could stratify who is at higher risk of developing an AAA. They identified genetic variants that raise the risk of abdominal aortic aneurysm by comparing more than 7,600 veterans with abdominal aortic aneurysm and more than 172,000 without the condition who were genotyped as part of the Million Veteran Program (MVP) of the U.S. Department of Veteran Affairs. The researchers identified 29 genetic mutations related to abdominal aortic aneurysm risk that are relatively common in the population and created a polygenic risk score, i.e., basically a way to add them all up to quantify how much risk an individual might have based on his genetics. In the study, among veterans 50 years of age and older who scored in the top 5% of genetic risk, 7.8% had been diagnosed with abdominal aortic aneurysm.

“I think this is the future of precision medicine—to use someone’s genetics to identify those at high risk and to screen and potentially treat them before it becomes a problem,” said Derek Klarin, M.D., lead author of the study and a vascular surgery fellow at the University of Florida College of Medicine in Gainesville, Florida. This  turned out to be slightly higher a risk than the 6-7% occurrence in men 65 and over who would be screened under the USPSTF’s recommendations.

Although the present study involved only veterans, the researchers obtained the same results when they repeated the analysis in a sample of Mayo Clinic patients and participants from two other biobanks. Because the database included primarily white men, the results may not be applicable to women and men from other ethnic groups. Importantly, there needs more research to be done to understand how best to identify women who will develop an abdominal aortic aneurysm. Also, some data on African-American veterans indicate that they in general are at lower risk and it seems that the genetics of the AAA in African Americans is not the same as in Caucasian individuals.

See here a short sequence on abdominal aortic aneurysms:

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Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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