Age, hypertension and arterial function.

1. Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross-sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age-related changes observed in peripheral arteries appear to be less marked. 2. The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3. Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4. Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end-product cross-links between proteins, such as collagen and elastin, hold substantial promise.