Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage

Abstract

Over the past decade, numerous studies have shown that increased aortic stiffness is associated with major cardiovascular disease end points, including heart disease, stroke, and kidney disease. Cardiac abnormalities and enhanced atherogenesis in the setting of increased pulsatile load on heart and arteries have been well described. However, recent studies have shown a further association between excessive pressure pulsatility and a number of afflictions of aging that share a predominant microvascular etiology, including many forms of kidney disease and cognitive impairment. In these disorders, microvascular remodeling and impaired regulation of local blood flow, which are related to large artery stiffness and pressure pulsatility, are associated with evidence of diffuse microscopic tissue damage. This brief review will summarize age-related changes in aortic and peripheral vascular function and will discuss potential mechanisms leading from changes in properties of large arteries to excessive pressure pulsatility, abnormal microvascular structure and function, and end-organ dysfunction and damage.

Fig. 1.

A brief synopsis of pulsatile hemodynamics. A: a simple model of the arterial system with a single dominant reflecting site at the interface between aorta and muscular arteries. When the forward wave (P_f) encounters the reflecting site, a portion is reflected (P_b) and most is transmitted (P_t). B: when the aorta stiffens (denoted by a thicker wall), impedance mismatch is reduced, the reflecting site shifts distally, a smaller fraction of P_f is reflected, and therefore more is transmitted into the microcirculation, which may trigger hypertrophic remodeling. C: the input flow wave interacts with input impedance (Z_i) to produce the resulting pressure wave. The forward-flow wave (Q_f) interacts with characteristic impedance (Z_c) to produce P_f. Wave reflection and overlap between P_f and P_b creates late systolic augmentation (P_aug), which contributes to central pulse pressure (CPP). The timings of wave reflection (t_i) and systolic ejection (t_es) are noted, and considerable overlap between P_f and P_b is evident (t_i < t_es). Total arterial compliance (TAC) can be computed by analyzing the pressure decay in diastole. PPP, peripheral pulse pressure. D: representative carotid (dark) and brachial (light) waveforms in a young healthy person. Note substantial amplification (Amp) of the pulse pressure with distal propagation. E: similar waveforms in an older individual with prominent central augmentation (Aug), which obscures normal peripheral amplification (Amp) of the forward-wave peak. [A and B reproduced with permission from Vyas et al. (96).]

Fig. 2.

A schematic representation of approximate patterns of change in key pulsatile hemodynamic measures with advancing age. Peripheral systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) all increase modestly before age 60 yr, whereas PPP falls slightly. During this early phase, augmentation index (AI) increases dramatically, whereas aortic and peripheral pulse wave velocity (PWV) change modestly. In contrast, after 60 yr of age, PPP increases dramatically and AI plateaus despite an ongoing increase in aortic PWV. At this transition point, aortic PWV meets then exceeds peripheral PWV, leading to a reduction in reflection at this junction (Fig. 1B), likely explaining the plateau in AI despite increasing aortic PWV.

Fig. 3.

Forearm vascular resistance (FVR) at rest (A) and during hyperemia (B) induced by 5 min of forearm ischemia. Data are least square means of natural log-transformed FVR, plotted according to tertiles of carotid-femoral PWV (CFPWV) and forward pressure wave amplitude, and adjusted for age, sex, body mass index, heart rate, total-to-high-density lipoprotein cholesterol ratio, triglycerides, fasting glucose, prevalent cardiovascular disease, diabetes, use of lipid-lowering or antihypertensive therapy, smoking, hormone replacement in women, timing of walk test. and daily aspirin use. [Reproduced with permission from Mitchell et al (65).]