Heart Disease Trigger May Be in Your Genes

Feb. 7, 2013— -- A type of cholesterol you've probably never heard of may be linked to the third leading cause of heart disease in the country.

In a study published Wednesday in the New England Journal of Medicine, a team of researchers from McGill University, Harvard, Johns Hopkins and other institutions report discovering an abnormality in the gene responsible for a little-known type of cholesterol called Lp(a). This form of cholesterol appears to cause a condition known as aortic stenosis, which affects 1.5 million Americans.

In aortic stenosis, the main valve regulating blood flow between the heart and the rest of the body can become critically narrowed. To better understand this, picture a room with a door that hangs on an old, creaky hinge so damaged by years of rust that it can only open a small crack. Now imagine what would happen if you and your friends all tried to squeeze out through the door at once, and you'll have an idea of the trouble blood cells have leaving the heart through a heavily calcified aortic valve.

Patients with aortic stenosis often lack symptoms until it reaches a critical stage marked by fainting, heart attacks or early death. On average, half of patients will die within two years once these symptoms develop, unless they undergo surgical correction.

In the new study, the authors found that people with a common genetic variant for Lp(a) have a 60 percent greater risk of developing aortic calcifications than others.

"We've all know that Lp(a) is strongly associated with an increased risk of heart attack for some time now," said the lead study author, Dr. George Thanassoulis of McGill University in Canada. "But now we can link it to heart valve disease for the first time.

"It is interesting that one molecule that we don't routinely screen for is linked to a number of cardiovascular diseases."

As for who should be screened for this type of cholesterol -- much as how patients are currently tested for "good" HDL and "bad" LDL cholesterol -- doctors are split.

"These results do not support widespread screening in and of themselves," Thanassoulis said, adding that although aortic stenosis is a common cardiac condition, it only affects 1 to 2 percent of the population. In other words, even patients with the genetic variation still only have a roughly one-in-30 lifetime chance of developing aortic stenosis.

Dr. Lori Mosca, director of Preventive Cardiology at NewYork-Presbyterian Hospital, said that because of this fact, she would only recommend such screening in those at a high risk for heart problems.

"Lp(a) is an inherited risk factor for premature heart disease that is not responsive to lifestyle interventions [like diet and exercise]," she said. "I consider measuring it if I have a patient with a personal or family history of premature heart disease or aortic stenosis."

These doctors say determining the level of this cholesterol could be important. Learning which patients have extremely high Lp(a) can help to better predict risk for heart attack in some individuals, according to a study published last month in the Journal of the American College of Cardiology by one of the new study's coauthors, Dr. Borge G. Nordestgaard. And even though Lp(a) can't be lowered by taking cholesterol-busting statins, European guidelines currently suggest treating patients with Lp(a) levels in the top 20 percent with niacin, another type of cholesterol lowering medication that they say may have some effect.

On the other end of the debate are doctors like Dr. Steven Nissen of the Cleveland Clinic, who said that even when someone has a high Lp(a) level, there is little evidence that lowering it would have a benefit.

"Although Niacin lowers Lp(a) a little bit, there are no outcome data suggesting a favorable effect," Nissen said.

Dr. Stephen Kopecky of the Mayo Clinic agreed. He said that when it comes to preventing heart disease, tried-and-true advice still applies.

"Too often, Americans may be looking for a quick fix that will allow us to trade in our bodies for new ones after 55 years or so," he said. "But there is still no substitute for trying to prevent all types of heart disease through improvements in our diet and exercise."