Do you wonder why some smokers develop heart disease, but others don’t? Or how someone who thrives on burgers and fries can live to be 90, when a vegetarian has a heart attack at 40?
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The answer may be in the genes. And the fact is, we are only beginning to understand how they affect our heart health.
“We all have abnormal genes called mutations, and some mutations make individuals susceptible to a disease,” explains W.H. Wilson Tang, MD, head of Cleveland Clinic’s Center for Clinical Genomics. “People think that if you have the mutation, you will get the disease, but that’s not necessarily true. Its effect is not always easy to predict.”
Take, for example, the mutation associated with hypertrophic cardiomyopathy, a disease that causes the heart muscle to become thick and stiff. “We only know of specific mutations in about half of individuals with the disease. Even those with similar mutations in the same proteins manifest the disease differently. That means other forces besides genes are at play,” says Dr. Tang.
“In fact, we are also beginning to understand that what we are exposed to—what we eat, or forces in our environment—appears to alter what our genes produce,” he says.
Genes and heart disease
In addition to hypertrophic cardiomyopathy, genetic abnormalities are known to cause Marfan syndrome and sudden cardiac death from long-QT syndrome.
Genes have been identified in many other rarer diseases that are passed down in families. Genetic tests are readily available when these problems are suspected.
Some genes, however, may not define a disease, but rather may identify a biological process that influences the development of a disease. Recently, researchers found an association between genetic abnormalities that cause elevated levels of two forms of cholesterol—low-density lipoprotein (LDL) and lipoprotein-a [Lp(a)]—and aortic stenosis, a disease that causes calcium buildup on the aortic valve. These abnormalities have been associated with coronary artery disease, but now it’s clear they may affect heart valves, as well.
“What the research hasn’t shown is whether the gene causes aortic stenosis. However, having those genes makes patients more vulnerable,” says Dr. Tang.
It might be a while before genetic tests to predict common heart diseases like aortic stenosis are developed, and even longer before clinicians determine which patients are most appropriate for testing.
Treating genetic diseases
A bigger issue than the ability to predict aortic stenosis is, if you learn you have the genetic mutation for high LDL or Lp(a), can you prevent the disease?
That’s a tough question to answer, says Dr. Tang. To date, researchers have been unable to prevent aortic stenosis using drugs that lower LDL known as statins. But that doesn’t mean the association between LDL and aortic stenosis is wrong.
“It could be a question of timing. Age always leads to a worse outcome. If the gene is discovered at age 60, statins may not work. We do not know whether they might prevent the disease if treatment is started at age 20,” he explains.
Medications aren’t always the answer, though.
“The promise of early identification in vulnerable patients will require a very different approach to prevention. We will need to change our behaviors to reduce risk factors long before any disease occurs,” says Dr. Tang.
Although other branches of medicine use genetic tests effectively to screen for and diagnose problems ranging from neurologic disorders to cystic fibrosis, genetic testing is still in its infancy.
“We are just scratching the surface, but we have a lot of hope,” says Dr. Tang
He anticipates that genetics will eventually change how cardiologists evaluate individuals and families with certain forms of heart disease. Take heart failure, for example. One in every five adults develops heart failure, and the disease affects the children of one of every four heart failure patients.
“When vulnerability is inherited, we would like to identify these patients before they develop heart failure. But even if we did, how would we act on the information?” asks Dr. Tang.
“Clinical knowledge is lagging behind technology. Catching up is one of the major goals of medical research in the coming decade,” he says. “It’s a daunting task, but an exciting one, and everyone is looking forward to seeing progress.”