Central-to-peripheral artery hemodynamics

High blood pressure (BP) is the leading modifiable risk factor for cardiovascular disease (CVD) and death. However, conventional brachial systolic and diastolic BP provide limited information on the underlying BP waveform and do not encompass all the cardiovascular risk associated with BP. Moreover, evidence suggests central (aortic) BP may be more clinically useful than conventional brachial BP, highlighting the importance of differences in central-to-peripheral vascular properties and arterial hemodynamics in the assessment of BP related risk. Recently, the reservoir-excess pressure model has emerged as a construct for deriving clinically relevant information from the underlying BP waveform and may be useful for assessing differences in central-to-peripheral artery hemodynamics. Nevertheless, there is an under-appreciation of the influence of differences in central-to-peripheral vascular properties on arterial hemodynamics and reservoir-excess pressure parameters. Consideration of the changes in vascular properties and a greater awareness of the hemodynamic variability throughout the arterial tree may facilitate a more accurate assessment of BP and BP related risk. Therefore, the broad aims of this research were to determine the hemodynamic differences between central and peripheral arteries and identify clinically useful parameters derived from arterial BP waveform analysis, with a particular focus on reservoir-excess pressure parameters. Evidence suggests the reservoir-excess pressure model has value for deriving physiological and clinically additive information from the underlying BP waveform. However, more research is needed to better understand the value of this model for the assessment of arterial hemodynamics and BP related cardiovascular risk. The reservoir excess pressure model is still in its relative infancy, and there is yet to be a published article that describes the physiological and clinical evidence relating to parameters derived via this model. This gap in the literature is addressed in chapter 1 as part of an invited review for the Journal of Frontiers in Physiology, where we highlight the need for greater appreciation of differences in central-to-peripheral artery hemodynamics and BP waveform morphology. Study 1 (Chapter 2) sought to determine the usefulness of the ratio of aortic-to-brachial artery stiffness (ab-ratio) for assessing central-to-peripheral artery properties. Previously, the ab-ratio has shown promise as a vascular risk marker independent of the influence of BP, but this has only been examined among individuals with disease. Study 1 found that in patients with disease, including renal disease (n=119), type two diabetes mellitus (n=77), and hypertension (n=140), the ab-ratio was not associated with BP (P >0.11 for all). Conversely, among healthy individuals (n=99), the ab-ratio was associated with BP (˜í‚⧠= 0.08, P = 0.003). These findings show that the ab-ratio is inherently related to BP and, thus, has limited potential as a tool for the assessment of vascular properties beyond techniques already available. In study 2 (Chapter 3), central-to-peripheral artery hemodynamics were assessed by examination of the differences in intra-arterial BP between the aortic, brachial, and radial arteries among 180 individuals undergoing coronary angiography. The key finding from this study was that systolic BP, the peak of the BP waveform, was, on average, 5.5 mmHg higher in the radial artery compared to the brachial artery accounting for 43% of the difference in systolic BP between the aorta and radial artery. There was significant between-person variability in the level of systolic BP difference between the brachial and radial arteries. Conversely, on average, there were small non-significant decreases for both diastolic and mean BP between the brachial and radial arteries (-1.1 and -1.6 mmHg, respectively). These findings improve our understanding of changes in central-toperipheral artery hemodynamics with implications for novel wrist-based BP devices and estimation of aortic BP via conventional pulse wave analysis methods. Additionally, the consistency of diastolic BP suggests a detailed analysis of diastolic BP waveform morphology via reservoir-excess pressure analysis, may present an opportunity asses central artery hemodynamics from the peripheral artery BP waveform. Study 3 (Chapter 4) sought to determine the uniformity and clinical value of key reservoir-excess pressure parameters derived from central and peripheral artery BP waveforms, with a focus on parameters relating to diastolic BP waveform morphology. Among 220 individuals undergoing a coronary angiography procedure, model parameters were derived from intra-arterial aortic, brachial, and radial BP waveforms, and clinical value was assessed by association with estimated glomerular filtration rate (eGFR). Of all the model parameters, the reservoir pressure and diastolic rate constant were the most uniform between arterial sites. However, only the diastolic rate constant had consistent associations with eGFR when derived from central and peripheral arteries (P <0.03). The diastolic rate constant, therefore, represents a clinically useful marker of BP related risk that, when derived from peripheral arteries, provides clinically important information related to central artery hemodynamics. Finally, study 4 (Chapter 5) examined the relationship of excess pressure to directly measured blood flow velocity. As predominantly a component of systolic BP waveform morphology, excess pressure is modified between central and peripheral arteries. Thus, it was unknown if previous observations of the equivalency of central artery excess pressure to aortic blood flow were applicable in peripheral arteries. Among 97 individuals, intra-arterial BP was recorded via a fluid-filled catheter, and flow velocity was measured via Doppler ultrasonography at the brachial and radial arteries. This study found that in both time and frequency domain analyses, excess pressure derived from brachial and radial arteries was analogous to blood flow velocity, thus affording the opportunity to derive information related to arterial flow using only the BP waveform. These findings are expected to have clinical utility as they may help refine methods for non-invasive hemodynamic monitoring used in the management of the critically ill. In summary, the ab-ratio has limited value as a marker of central-to-peripheral vascular properties as shown in study 1. The second study is the first sufficiently large and robust investigation of central-to-peripheral intra-arterial BP differences, where it was found that the systolic component of BP waveform morphology is, on average, amplified, albeit with major inter-individual variability. Conversely, in study 3 it was discovered that the diastolic rate constant, a parameter derived via the reservoir-excess pressure model related to diastolic waveform morphology, was uniform in both absolute value and association with risk when derived from central and peripheral arteries and may facilitate the assessment of risk related to central artery hemodynamics. Finally, study 4 showed that excess pressure derived from peripheral artery BP waveforms was analogous to flow velocity and may lead to improvements in non-invasive hemodynamic monitoring applicable to the clinical setting. Altogether, this thesis provides a body of new information on central-to-peripheral artery hemodynamics and identifies clinically useful parameters derived from reservoir-excess pressure analysis of the underlying BP waveform. These findings could lead to real-world improvements in the assessment of BP related cardiovascular risk and better BP risk phenotyping.