Gene tied to cholesterol that harms heart

MCGILL U. (CAN) — Researchers have uncovered a link between a gene and a type of cholesterol that increases the risk of developing the most common form of heart valve disease by more than half.

The results of the study, published in the New England Journal of Medicine, point to the first known cause of aortic stenosis, which affects more than 5 million people in North America, and to a potential treatment.


“We found that an unusual type of cholesterol called lipoprotein (a) or Lp(a)—that is not normally screened for in current clinical practice—appears to be a cause of aortic valve disease,” says George Thanassoulis, assistant professor of medicine at McGill University.

“High levels of this type of cholesterol are predicted primarily by an individual’s genetic make-up with only modest influence from lifestyle or other factors.”

Aortic stenosis (AS) is the third most prevalent form of cardiovascular disease in the western world, after hypertension and coronary artery disease. It mainly affects people over the age of 60 years.

AS is caused by calcification and hardening of the aortic valve which impedes blood flow from the heart to the rest of the body leading to chest pain, loss of consciousness and shortness of breath.

In severe cases, patients need aortic valve replacement surgery. Currently, there are no medical treatments to prevent this disease or reduce the need for valve replacement.

According to the study’s lead investigators. the findings not only explain why heart valve calcification may run in families, but could also lead to the development of targeted medications that might slow the progression of valve disease and reduce the need for valve surgery in patients.

“Previous studies could not differentiate whether Lp(a) was a cause or simply a marker of valve disease,” says Thanassoulis. “But our results strongly suggest a causal link and add to the mounting evidence that Lp(a) may be an important drug target for cardiovascular diseases.”

“This is an important step forward in understanding the biology of the development of aortic stenosis and how this common genetic variant, which is found in thirteen percent of the general population, contributes to that risk,” says Wendy Post, a cardiologist and associate professor of medicine and epidemiology at Johns Hopkins University School of Medicine. “Advancing age is a major risk factor for aortic stenosis and, with the aging population, this will become an even bigger health concern.”

Frequently used statin medications, which reduce the common form of cholesterol that blocks arteries, do not reduce Lp(a) or prevent aortic valve calcification. “Therefore, it is very important that these results benefit our patients,” says Thanassoulis.

“For this to happen we need to test whether lowering this type of cholesterol with other drugs slows valve calcification in a randomized clinical trial. Our hope is to eventually prevent valve disease with medication and reduce the need for surgery.”

The Canadian Institutes of Health Research, the National Heart, Lung, and Blood Institute, the Fonds de recherche du Québec-Santé, the Royal College of Physician and Surgeons of Canada, the Association des Cardiologues du Québec, and the Montreal General Hospital Foundation of the MUHC helped fund the research.

Source: McGill University (CA)