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 and mortality. We briefly review the epidemiological evidence and discuss in more detail the pathophysiological basis for this observation and the therapeutic consequences. We focus on the vascular determinants of increased pulse pressure. Both longitudinal and cross-sectional components of the vascular system contribute to the shape of the arterial pressure wave and, thereby, to pulse pressure. The primary longitudinal component is the architecture of the arterial tree, which determines the major reflection sites for the pressure wave. The cross-sectional architecture of the vascular system consists of a geometric (diameter) and a structural (composition vessel wall) component. Both diameter and composition of the vessel wall vary greatly when going from central to more peripheral arteries. We review the implications for the functional properties of various arterial segments. Finally, we discuss the therapeutic consequences of targeting pulse pressure rather than mean blood pressure with various drug classes. Among the antihypertensive agents, nitrates, NO donors, and drugs that interfere with the renin-angiotensin-aldosterone system may offer useful tools to lower pulse pressure, in addition to mean blood pressure. Future developments may include non-antihypertensive agents that target collagen or other components of the arterial wall matrix. However, large-scale clinical trials will have to confirm the therapeutic value of these agents in the treatment of increased pulse pressure and arterial stiffness.