Arteriosclerosis

Abstract

See related article, pp 123–128 Over the last 20 years, aortic stiffness has emerged as an important, independent predictor of cardiovascular outcome. Recent data suggest that it may add to existing risk prediction models and improve patient stratification. However, the precise biological pathways and processes underlying aortic stiffening remain unclear. A better understanding of these is an important prerequisite for the rational design of novel antistiffening drugs, which may prove valuable in reducing cardiovascular risk, particularly in those individuals with stiff arteries. In almost all populations, aortic stiffness is positively correlated with age, and in multiple regression analyses age is invariably the dominant determinant of stiffness.1 Consequently, age-related aortic stiffening (arteriosclerosis) is often considered to be inevitable. The process underlying arteriosclerosis is generally believed to be fatigue fracture of elastic fibers within the arterial wall. As such, age is actually a surrogate for cycle number (ie, number of heart beats), which, together with the level of cyclic stress (pulse pressure), determines the rate of elastic fiber degeneration. To a limited extent, this view has been substantiated by animal studies, and our own recent observations in the Caerphilly Heart Study.2 We found that the heart rate pulse pressure product, integrated over a 20-year follow-up period, was independently correlated with current aortic pulse wave velocity (aPWV). However, this cannot be the whole story, not least because the correlation that we observed was quite modest, and several other lines of evidence strongly suggest that arteriosclerosis is more pathological than …