October 26th, 2014

Genetic Study Suggests Possible Causal Role for LDL in Aortic Valve Disease

Although LDL is an important risk factor for aortic valve disease, the precise role it plays has been uncertain. Lipid-lowering therapy in people with established aortic valve disease has not been shown to be beneficial. Now, however, a new genetic study published in JAMA suggests that LDL cholesterol may in fact cause an increase in aortic valve calcium and aortic valve stenosis. This may mean that LDL-lowering therapy could prove beneficial when given earlier in the disease process.

Researchers in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium used Mendelian randomization to assess in nearly 7,000 people the association of a genetic risk score with the presence of aortic valve calcium. They found a strong association between the genetic risk score for LDL and the presence of aortic valve calcium.

The researchers also analyzed data from more than 28,000 participants in the the Malmö Diet and Cancer Study (MDCS). The genetic risk score for LDL was significantly associated with the incidence of aortic stenosis as ascertained from national registries.

“Our findings link a genetically mediated increase in plasma LDL-C with early subclinical valve disease, as measured by aortic valve calcium, and incident clinical aortic stenosis, providing supportive evidence for a causal role of LDL-C in the development of aortic stenosis,” write the authors. The authors speculate that LDL lowering may not be effective in established valve disease “once valve calcification and remodeling are well established…” But, they write, “our results suggest that early lipid lowering, prior to the development of even mild forms of aortic stenosis, may be required to prevent aortic valve disease.”


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