Whereas large arteries dampen oscillations resulting from intermittent ventricular ejection, small arteries steadily deliver optimal blood flow to various organs as the heart. The transition from pulsatile to steady pressure is influenced by several factors as wave travel, damping and reflections, which are mainly determined by the impedance mismatch between large vessels and arteriolar bifurcations. The mechanism(s) behind the dampening of pressure wave in the periphery and the links between central and peripheral pulsatile pressure (PP) may determine cardiac damage. Active pathways participate to pulse widening and changes in pulse amplitude in microvessels. Steady and cyclic stresses operate through different transduction mechanisms, the former being focal adhesion kinase, and the latter free radicals and oxidative stress. Independently of mechanics, calcifications and attachment molecules contribute to enhance vessel-wall stiffness through changes in collagen cross-links, proteoglycans, integrins and fibronectin. Enhanced PP transmission may thus occur and precipitate organ damage at each time autoregulatory mechanisms normally protecting the heart from vascular injury are blunted. Such circumstances, observed in old subjects with systolic hypertension and/or diabetes mellitus type 2, particularly under high sodium diet, cause cardiac damage and explain why increased PP and arterial stiffness are significant predictors of morbid-mortality in the elderly.