• aortic valve stenosis
• transcatheter aortic valve replacement

Over the last decade, it has become increasingly clear that different mechanisms drive the development of native aortic stenosis. Most patients who develop native aortic stenosis have hypertension, and some have increased cholesterol. However, male sex, body mass index, smoking, metabolic syndrome, renal failure and genetic factors (eg, bicuspid aortic valve) have been identified in epidemiological studies as risk factors for developing native aortic stenosis. These studies have led to a series of clinical variables, which provide the foundation for understanding the mechanisms. The low-density lipoprotein (LDL) radius theory gives a framework for understanding the development of native aortic stenosis.1 In native aortic stenosis, LDL-cholesterol insudates into endothelial cells, resulting in an inflammatory reaction forming increased oxidised phospholipids, leading to osteogenesis. This process is further propagated by high blood pressure; in patients with asymptomatic mild-to-moderate aortic stenosis, blood pressure levels around 130–139 mm Hg/70–90 mm Hg have improved outcomes compared with higher blood pressure levels.2

Although the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study did not show a benefit for reducing LDL-cholesterol on the progression of native aortic stenosis, a following subanalysis reported by Greve et al discovered that a reduction of LDL-cholesterol in patients with LDL-cholesterol above the median did reduce the progression of aortic stenosis.3 The lesson from this subanalysis suggested that interventional pharmacological treatment must focus on the mechanisms driving the development of aortic stenosis. That is, lowering LDL-cholesterol does not prevent the progression of native aortic stenosis in patients with normal LDL-cholesterol and other mechanisms that drive aortic stenosis progression.

A decade ago, Thanassoulis et al discovered that the role of genetic …