Triangulating the peaks of arterial pressure.

Increased arterial stiffness and excessive pressure pulsatility have emerged as important risk factors for a number of common disorders of aging, including cardiovascular disease, stroke, cognitive impairment, and renal disease. The triple-threat combination of robust associations between arterial stiffness and the foregoing disorders, a marked increase in arterial stiffness with advancing age and the graying of our society, has led to intensive efforts to identify mechanisms that contribute to arterial stiffening and widening pulse pressure to define interventions to prevent or reverse stiffness and potentially reduce the substantial burden of related disease. Wave reflections complicate the task of evaluating arterial hemodynamics and play an unclear role in the foregoing diseases. When the heart ejects, ventricular outflow interacts with characteristic impedance of the proximal aorta to produce the forward pressure wave, which travels down the normally compliant aorta at a finite pulse wave velocity (PWV). When the forward wave encounters impedance mismatch, such as a branch point or a change in diameter or wall properties, a partial reflection occurs. Innumerable reflections arising from locations distributed throughout the arterial tree summate into a remarkably discrete reflected pressure wave with amplitude 40% of the incident wave. The summated reflected wave returns to the central aorta in midsystole, creating an inflection point and secondary late systolic pressure rise that often augments central aortic systolic and pulse pressure.1 Variable timing of this retrograde-traveling reflected wave creates regional inequalities in systolic and pulse pressure and, therefore, complicates interpretation of single point pressure measurements, such as standard brachial blood pressure, which may differ from central aortic pressure. Augmentation index (AI), which expresses late systolic pressure augmentation as a percentage of pulse pressure, is frequently used to assess wave reflection (Figure). AI, which depends on both timing and amplitude of the reflected wave, has also been widely cited as a measure of arterial stiffness based on the assumption that increasing PWV leads to progressively earlier wave reflections from a relatively fixed reflecting site. The resulting progressive systolic overlap of the forward and reflected wave has been proposed as the principal determinant of increasing pulse pressure with advancing age.2 However, recent community-based studies have challenged these seemingly straightforward assumptions.3,4 Timing of wave reflection is related to PWV and the distance to the “effective” reflecting site. A typical aortic PWV of 6 to 7 m/s and roundtrip reflected wave transit time of 120 to 150 ms suggests that the effective reflecting distance (ERD) is 40 to 50 cm from the heart in healthy young women and men, respectively. However, rather than vary inversely with PWV, timing of wave reflection hovers in a relatively narrow range (110 to 150 ms) across the full human life span, despite a major ( 3-fold) increase in aortic PWV.3–5 Minimally changing reflected wave transit time in the presence of a marked increase in aortic PWV indicates that ERD increases substantially with age. ERD lengthens in children because of an increase in body size. In middle-aged and elderly individuals, ERD lengthens because the aorta, which is normally much more compliant than the muscular arteries, becomes as stiff as the muscular arteries by 50 to 60 years of age. This “impedance matching” between aorta and muscular arteries reduces proximal wave reflection and shifts reflecting sites downstream.3 Loss of proximal wave reflection implies increased transmission of pulsatility into the periphery, potentially causing damage, unfavorable remodeling, and impaired flow reserve.6 Because of the foregoing effects of age on timing and amplitude of wave reflection, AI has complex relations with age. AI falls slightly with growth during childhood, increases rapidly between 20 and 40 years of age, and then plateaus or falls beyond 60 years of age.3–5 In contrast, pulse pressure, aortic PWV, and forward wave amplitude increase modestly before 40 years of age and then dramatically after 60 years of age, when cardiovascular risk increases exponentially. Thus, excessive wave reflection is unlikely to explain a major component of age-related increases in pulse pressure. AI is lower in men than women and is reduced in the presence of obesity, diabetes, and higher heart rate, despite elevated PWV.7,8 AI is also lower in individuals with impaired left ventricular function despite normal or increased wave reflection, because the failing heart cannot augment pressure in the face of a late systolic increment in load.9 Accumulation of these risk factors with age may contribute to the plateau or fall in AI in the elderly. Complex relations with age and inverse relations with several major cardiovascular disease risk factors may limit the use of AI for risk stratification in the general population. Furthermore, dependency of AI on multiple factors has clouded our understanding of changes in wave reflection with advancing age. In this issue of Hypertension, Westerhof et al10 describe a new tool that may help deconvolve some of the complex dependencies of AI on timing and amplitude of the reflected wave and duration and pattern of systolic ejection. The approach is straightforward and logical. To assess forward and reflected wave amplitude, pressure and flow waveforms are both required. When the reflected wave returns to the heart during systole, as is The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From Cardiovascular Engineering, Inc, Waltham, Mass. Correspondence to Gary F. Mitchell, Cardiovascular Engineering, Inc, University Office Park, Building 2, 51 Sawyer Rd, Suite 100, Waltham, MA 02453. E-mail [email protected] (Hypertension. 2006;48:543-545.) © 2006 American Heart Association, Inc.