Promising research in mice has led to hopes that a common blood pressure drug may block some of the worst effects of Marfan's syndrome, a genetic disease that seriously weakens the main artery, the aorta. The research was published April 6 in the journal Science, the Associated Press (AP) reported. Both pregnant and "teenage" mice genetically engineered to have a form of Marfan's syndrome were given either losartan (Cozaar) or another type of blood pressure pill. Newborn mice had no aortic damage and the "teenagers" were healed within six months, AP reported. A human study is expected to begin soon.
By Howard LeWine, M.D.
Harvard Medical School
What Is the Doctor's Reaction?
It's rare for results of a study done on mice to have immediate potential applications for humans. The "Marfan's" mouse study reported in Science hits this mark. The very positive effect of the commonly used blood pressure medication losartan (Cozaar) on the Marfan's mouse makes this an appealing consideration for some people affected by Marfan's syndrome.
Marfan's syndrome is a genetic disorder that alters the structure of connective tissue. Connective tissues have qualities like heavy-duty bungee cords; these tissues are strong, with some elasticity. Connective tissues make up the tendons, ligaments, cartilage and walls of large arteries such as the aorta.
People with Marfan's don't make normal amounts of a protein called fibrillin, which is a key component of the elastic fibers in connective tissue. Without normal fibrillin, the supporting structures in the body can weaken over time and result in multiple medical problems.
The typical appearance of a person with Marfan's is someone who is tall, with long limbs and long fingers. However, many people with the disorder do not have the classic appearance, even though their connective tissues are weak and less elastic.
A primary concern in people with Marfan's is the risk of aortic aneurysm and heart valve abnormalities. Blood exiting the heart hits the first part of the aorta under great pressure. This section of the aorta (the aortic root and ascending aorta) relies on strong, elastic fibers to accept those high pressures for a lifetime. Without normal fibrillin, the walls of the aortic root and ascending aorta weaken and expand, forming an aneurysm. The larger the aneurysm, the more likely it is to rupture.
What Changes Can I Make Now?
The degree of fibrillin abnormality in people with Marfan's syndrome is highly variable. Some people are at very low risk of major complications, while others, even in the same family, may have an abnormal aorta or heart valve at a young age. People suspected of having Marfan's syndrome based on their physical appearance, and family members of people with Marfan's syndrome are screened with heart ultrasounds and CT scans to check the size of their aortic roots.
If a person with Marfan's syndrome has high blood pressure or even a slightly dilated aortic root, the person usually is advised to take a beta-blocker such as atenolol or metoprolol. This reduces the thrust of blood pushing out against the first section of aorta. Strenuous exercise and weightlifting probably should be avoided.
There is some debate about how much to let an aortic root expand before recommending surgery to repair it. The standard size has been around 5 centimeters or greater. However, some surgeons are recommending repair at more than 4 centimeters. What may be even more important than size at any one time is the change in size over time. People with Marfan's syndrome need to have regularly scheduled tests to measure their aortic root to look for signs of expansion from one year to the next.
What Can I Expect Looking to the Future?
The "Marfan's" mouse study suggests that losartan (Cozaar) actually may improve the structure of the abnormal connective tissue in this disorder. If this is the case, the cause of Marfan's may be more complicated than just a deficiency of fibrillin.
A study of losartan in children will be getting under way later this year. Meanwhile, for some children and adults with Marfan's and higher-than-desired blood pressures, losartan with a beta-blocker appears to be an attractive combination.
