Aging is Associated With an Earlier Arrival of Reflected Waves Without a Distal Shift in Reflection Sites

Background: Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (T_INF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a "distal-shift" of reflection sites. T_INF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results: We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTT_WSA) and partially distributed tube-load (TL) modeling (RWTT_TL). Consistent with previous reports, T_INF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTT_WSA (general population -15.0 ms/decade, P<0.001; clinical population -9.07 ms/decade, P=0.003) and RWTT_TL (general -15.8 ms/decade, P<0.001; clinical -11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. T_INF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions: RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging.