Disease prevention

Calcific aortic stenosis is due to an active disease process at the cellular and molecular levels (FIGURE 2 Disease Mechanisms and Time Course of Calcific Aortic Stenosis.).

Differences between disease initiation and progression that are observed at the tissue level are also seen in studies showing that clinical factors associated with the early stage of the disease process differ from those associated with progression. For example, although elevated serum lipid levels are associated with aortic-valve sclerosis, there is no convincing evidence that elevated serum LDL levels are associated with more rapid disease progression. Similarly, systemic markers of inflammation are not associated with progression of aortic-valve disease. Transformation at the tissue level from early to progressive disease probably explains why prospective, randomized clinical trials of lipid-lowering therapy in adults with mild-to-moderate aortic stenosis showed no significant effect on disease progression or aortic-valve events.

Once leaflet disease is present, hemodynamic progression is associated with older age, male sex, the severity of stenosis, and the degree of leaflet calcification. Progression from aortic sclerosis to valve obstruction occurs in only about 10 to 15% of patients over a period of 2 to 5 years. Once even mild valve obstruction is present, progressive stenosis occurs in nearly all patients, and most of them eventually require valve replacement. On average, the maximum transvalvular velocity increases by 0.1 to 0.3 m per second per year, with the mean gradient increasing by 3 to 10 mm Hg per year and the valve area decreasing by 0.1 cm² per year. These average values are somewhat helpful in counseling patients but do not allow precise prediction of when aortic-valve replacement will be needed, because hemodynamic progression varies widely among patients and often accelerates as stenosis becomes more severe. The degree of aortic stenosis associated with the onset of symptoms also differs among patients, with some patients remaining asymptomatic for several years despite hemodynamically severe disease.

Increased understanding of the specific disease pathways involved in calcific valve disease, the clinical and genetic associations with aortic stenosis, and the observed natural variation in disease progression all suggest that medical therapy might prevent or delay disease progression. In addition to lifestyle and pharmacologic interventions to reduce cardiovascular risk, treatment might be targeted to specific cellular and molecular pathways at various time points in the disease process, including pathways involved in oxidative stress, the renin–angiotensin system, and triggers of abnormal tissue calcification. However, at present no medical therapies have been shown to prevent disease progression.