Statins show promise as an aid in controlling heart valve disease
By Ronald Kotulak
Tribune science reporter
Published April 12, 2006
Heart valve disease, which leads to 100,000 open heart surgeries a year in the U.S., may be preventable, according to research conducted at Northwestern Memorial Hospital.
Long thought to be the result of wear and tear, for which surgery was the only remedy, heart valve disease now appears to be caused by a potentially reversible chronic inflammatory process, said Dr. Nalini Rajamannan, director of the hospital's center for heart valve disease in the Bluhm Cardiovascular Institute.
Studies in rabbits that develop a similar type of heart valve disease after being fed a high fat diet showed that the family of anticholesterol drugs known as statins reversed some of the disease, Rajamannan said.
"Our findings open the door to the idea that medical therapies such as statins may be able to play a role in preventing or slowing the process and curtailing the need for surgery," said Rajamannan, also a faculty member at Northwestern University's Feinberg School of Medicine.
Genetic and chemical analyses of damaged tissue show that heart valves become stiff and inflexible and begin to leak or malfunction when their genetic programming goes haywire and starts producing cartilage or bone, Rajamannan reported in the online version of the Journal of the American College of Cardiology.
A high-fat diet, the main risk factor in heart disease, also appears to cause valvular disease, she said. The disease process then sets up chronic inflammation in the valves that inappropriately turns on genes that should remain turned off, she said.
Inflammation in the mitral valve turns on genes that produce cartilage like that found in the knee joint, Rajamannan said. In the aortic valve, which is exposed to a stronger flow of blood, abnormal gene activity produces bone tissue, she said.
Dr. Roberto Lang, a University of Chicago heart specialist who was not involved in the study, said the findings were promising because they opened the door to treating the most common causes of valve disease with medications. But, he said, further studies are needed to determine how effective medical treatment might be.
Doctors commonly describe diseased valves, which appear hardened and whitish, as calcified because of the calcium they contain. The buildup of calcium was considered to be a mechanical process of aging.
Rajamannan said she began studying diseased valves because she suspected there might be an underlying biological process causing the damage.
The disease processes either cause valves to leak or to limit the flow of blood through the heart, which normally pumps about 100 gallons of blood every hour. A diseased mitral valve can provoke irregular heartbeats known as atrial fibrillation, which can cause strokes or heart failure. Aortic valve disease also can cause heart failure in addition to arrhythmia, infection and sudden death.
"Once we know the pathways and mechanism of valvular disease, then we can try out therapeutic measures to prevent it," said Dr. Shahbudin Rahimatolla, a University of Southern California cardiologist and a study co-author who is one of the world's leading experts on valvular disease.
Besides statins, new drugs may be developed that stop the abnormal activity of the cartilage and bone genes, he said.
Rajamannan said the next step would be a study in which patients with early valve disease are put on statins to determine if the disease process can be slowed or stopped. Her research is supported by more than $750,000 in grants from the National Institutes of Health and the American Heart Association.
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By Ronald Kotulak
Tribune science reporter
Published April 12, 2006
Heart valve disease, which leads to 100,000 open heart surgeries a year in the U.S., may be preventable, according to research conducted at Northwestern Memorial Hospital.
Long thought to be the result of wear and tear, for which surgery was the only remedy, heart valve disease now appears to be caused by a potentially reversible chronic inflammatory process, said Dr. Nalini Rajamannan, director of the hospital's center for heart valve disease in the Bluhm Cardiovascular Institute.
Studies in rabbits that develop a similar type of heart valve disease after being fed a high fat diet showed that the family of anticholesterol drugs known as statins reversed some of the disease, Rajamannan said.
"Our findings open the door to the idea that medical therapies such as statins may be able to play a role in preventing or slowing the process and curtailing the need for surgery," said Rajamannan, also a faculty member at Northwestern University's Feinberg School of Medicine.
Genetic and chemical analyses of damaged tissue show that heart valves become stiff and inflexible and begin to leak or malfunction when their genetic programming goes haywire and starts producing cartilage or bone, Rajamannan reported in the online version of the Journal of the American College of Cardiology.
A high-fat diet, the main risk factor in heart disease, also appears to cause valvular disease, she said. The disease process then sets up chronic inflammation in the valves that inappropriately turns on genes that should remain turned off, she said.
Inflammation in the mitral valve turns on genes that produce cartilage like that found in the knee joint, Rajamannan said. In the aortic valve, which is exposed to a stronger flow of blood, abnormal gene activity produces bone tissue, she said.
Dr. Roberto Lang, a University of Chicago heart specialist who was not involved in the study, said the findings were promising because they opened the door to treating the most common causes of valve disease with medications. But, he said, further studies are needed to determine how effective medical treatment might be.
Doctors commonly describe diseased valves, which appear hardened and whitish, as calcified because of the calcium they contain. The buildup of calcium was considered to be a mechanical process of aging.
Rajamannan said she began studying diseased valves because she suspected there might be an underlying biological process causing the damage.
The disease processes either cause valves to leak or to limit the flow of blood through the heart, which normally pumps about 100 gallons of blood every hour. A diseased mitral valve can provoke irregular heartbeats known as atrial fibrillation, which can cause strokes or heart failure. Aortic valve disease also can cause heart failure in addition to arrhythmia, infection and sudden death.
"Once we know the pathways and mechanism of valvular disease, then we can try out therapeutic measures to prevent it," said Dr. Shahbudin Rahimatolla, a University of Southern California cardiologist and a study co-author who is one of the world's leading experts on valvular disease.
Besides statins, new drugs may be developed that stop the abnormal activity of the cartilage and bone genes, he said.
Rajamannan said the next step would be a study in which patients with early valve disease are put on statins to determine if the disease process can be slowed or stopped. Her research is supported by more than $750,000 in grants from the National Institutes of Health and the American Heart Association.
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