Gene variant increases risk of heart valve disease

A variant of the gene for a type of cholesterol called lipoprotein(a) (Lp(a)) is linked to heart valve disease, according to a large international study. The study, carried out by the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, found those with the variant had elevated blood levels of Lp(a) and an increased risk of aortic stenosis.

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

Aortic stenosis affects two to seven percent of Europeans over the age of 65. It is caused by the build up of calcium in the hearts aortic valve, through which blood leaves the heart. This results in hardening and narrowing of the valve, resulting in symptoms such as shortness of breath, chest pain and eventual heart failure, stroke or sudden cardiac death.

Researchers analysed 2.5 million known genetic variants in the genomes of 7,000 Caucasians and found the Lp(a) variant was significantly associated with aortic stenosis, as assessed using computerised tomography (CT) scans. The findings were confirmed in a further 6,000 participants of Hispanic, African-American and Chinese-American descent.

'What makes these findings provocative is that we linked the genetic variant with a physiological change in lipoprotein levels... and fully diagnosed aortic valve disease, across multiple ethnicities', said senior director for genome research at the National Heart, Lung and Blood Institute, Maryland, USA, Dr Christopher O’Donnell, who was involved in the study.

Dr Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital, who was not involved in the study, told ABC News: 'Lp(a) is an inherited risk factor for premature heart disease that is not responsive to lifestyle interventions [like diet and exercise]. I'd consider measuring it if I have a patient with a personal or family history of premature heart disease or aortic stenosis'.

Currently the only available treatment for aortic stenosis is valve replacement. 'No medications tested to date have shown an ability to prevent or even slow progression', said Dr O'Donnell. 'By identifying for the first time a common genetic link to aortic stenosis, we might be able to open up new therapeutic options'.

The study was published in the New England Journal of Medicine.