Calcific Aortic Valve Disease: Insights Into the Genetics of Vascular Ageing.

The shifting global demographic profile toward an older population is well recognized and carries with it the increased burden of degenerative cardiovascular disease, with associated morbidity, mortality, and healthcare costs. Vascular ageing is characterized by increased arterial stiffness, systolic arterial hypertension, myocardial thickening and fibrosis, and associated atherosclerosis.1 See Article by Martinsson et al Calcific aortic valve stenosis (CAVS) is another manifestation and affects ≈1 in 30 people aged 75 years. Furthermore, CAVS is associated with several adverse vascular risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus, as well as with underlying structural abnormalities, for example, bicuspid aortic valve. Considerable resources are already devoted to health care consequent on vascular ageing and the load is increasing—as evidenced by the burgeoning need for operative and percutaneous aortic valve replacements.2 If society is to better manage health costs for the older population, we need to better understand the mechanisms of vascular ageing and thereby develop and implement novel preventive strategies. There is significant familial risk for atherosclerotic vascular disease, beyond familial hypercholesterolemia and hypertension, although the actual genetic factors responsible remain elusive. In this issue of Circulation: Cardiovascular Genetics , Martinsson et al3 present evidence for a significant familial risk for CAVS in the general population. At the same time, there is also a lesser, but nonetheless significant, environmental risk. The fascinating question is how we might explain these observations and whether we can now begin to formulate a hypothesis about why some individuals develop CAVS. A systolic ejection murmur is a common finding in older patients and echocardiography has shown us that most individuals develop some thickening and restriction of leaflet motion of the aortic valve with increasing age. Despite this, most …