Pulse pressure, arterial stiffness, and drug treatment of hypertension

Epidemiological studies in the past decade have stressed the importance of pulse pressure as an independent risk factor for cardiovascular morbidity a nd mortality. We briefly review the epidemiological evidence and discuss in more detail the pathophysiological basis for this observation and the ther apeutic consequences. We focus on the vascular determinants of increased pu lse pressure. Both longitudinal and cross-sectional components of the vascu lar system contribute to the shape of the arterial pressure wave and, there by, to pulse pressure. The primary longitudinal component is the architectu re of the arterial tree, which determines the major reflection sites for th e pressure wave. The cross-sectional architecture of the vascular system co nsists of a geometric (diameter) and a structural (composition vessel wall) component. Both diameter and composition of the vessel wall vary greatly w hen going from central to more peripheral arteries. We review the implicati ons for the functional properties of various arterial segments. Finally, we discuss the therapeutic consequences of targeting pulse pressure rather th an mean blood pressure with various drug classes. Among the antihypertensiv e agents, nitrates, NO donors, and drugs that interfere with the renin-angi otensin-aldosterone system may offer useful tools to lower pulse pressure, in addition to mean blood pressure. Future developments may include non-ant ihypertensive agents that target collagen or other components of the arteri al wall matrix. However, large-scale clinical trials will have to confirm t he therapeutic value of these agents in the treatment of increased pulse pr essure and arterial stiffness.