CardioExchange Archive

A genetic component is believed to play an important role in valvular heart disease, but the specific genes involved have not been identified. Now an interntional group of researchers has identified genetic variations that increase the risk for valvular calcification.

In an article published in the New England Journal of Medicine, members of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium report on their search for genes associated with aortic valve calcification and mitral annular calcification in several study cohorts. They found one SNP, in a gene previously shown to be associated with lipoprotein(a) levels and the risk for coronary artery disease, to be significantly associated with a doubling of the risk for aortic-valve calcification. This finding was replicated in additional cohorts.

Previous studies that linked Lp(a) with aortic valve disease could not sort out whether Lp(a) “was a cause or simply a marker of disease,” the authors write. The new findings, they claim, “provide evidence for a causal relationship between Lp(a) and calcific aortic-valve disease and strongly implicate genetic variation at the LPA locus in the pathogenesis of the disease.”

Although the researchers focused on aortic calcification as a marker for clinical aortic disease, they found that variations in the LPA genotype were associated with aortic stenosis and aortic-valve replacement. “Our results suggest that lifelong elevations in Lp(a) levels lead to a markedly increased prevalence of aortic-valve calcification in adulthood and implicate Lp(a) in the development of aortic-valve disease.”

The group also identified two SNPs associated with mitral annular calcification, but this finding could not be consistently replicated.

The researchers noted that additional studies will be required “to evaluate whether lowering Lp(a) levels will reduce the incidence or progression of aortic-valve disease.”

An NHLBI press release included this statement from coauthor Christopher O’Donnell, the NHLBI’s senior director for genome research: “No medications tested to date have shown an ability to prevent or even slow progression of aortic stenosis, and treatments are limited beyond the major step of replacing the aortic valve. By identifying for the first time a common genetic link to aortic stenosis, we might be able to open up new therapeutic options.”