High arterial blood pressure (BP) is a major global healht issue. Increased central pulse pressure (cPP) - the amplitude of the aortic BP wave - is a major cause of incident hypertension in middle-aged to older adults. Our research employs haemodynamic analysis to (i) identify and quantify cardiovascular contributions to cPP and its amplification to peripheral sites (where BP is typically measured), and (ii) uncover mechanisms driving increased pulse pressure.

We have indentified ventricular dynamics and aortic stiffness as key drivers of elevated pulse pressure in hypertension. In the absence of pharmacological agents targeting arterial stiffness, modulating ventricular dynamics offers a promising approach for preventing or treating systolic hypertension. Additionally, ventricular dynamics is a main determinant of pulse pressure amplification, presenting an opportunity for noninvasive assessment of ventricular health through peripheral pulse wave analysis. Our key findings include:

1. Ventricular contractility plays a key role in raising and amplifying PP, by altering aortic flow wave morphology (Front Cardiovasc Med, 2023);

2. cPP is mainly determined by total arterial compliance (inversely associated with central arterial stiffness) and ventricular ejection dynamics: the volume of blood ejected by the ventricle into the aorta up to time of peak pressure and blood flow into the aorta up to this time point (Hypertension, 2017);


3. Ventricular dynamics account for a relatively large proportion of cPP increases, suggesting that cardiac dynamics are as relevant as vascular properties. Pressure wave reflection from the vasculature contributes minimally, indicating the need to incorporate cardiac properties into treatment strategies (Front Cardiovasc Med, 2023);

4. Increased cPP during inotropic stimulation and essential hypertension is primarily driven by the forward pressure wave (Hypertension, 2014), rather than by its reflection from the peripheral vasculature (Hypertension, 2017). This highlights the critical role of ventricular dynamics and proximal aortic pulse wave velocity as key determinants of cPP variation;


5. Pressure wave generation and reflection at the aortic root can be quantified using a time-varying emission coefficient, directly proportional to aortic flow, with its peak rising as cPP increases. Ventricular-aortic coupling is the main determinant of cPP elevation (IEEE Trans Biomed Eng, 2021);

6. The age-related increase in cPP is driven mainly by rising aortic stiffness and altered ventricular ejection patterns, suggesting that interventions affecting cardiac function may alter pulse wave morphology independently of arterial function (Hypertension, 2019);


7. Ventricular dynamics are crucial for pulse pressure amplification to the periphery, as demonstrated in vivo (Front Cardiovasc Med, 2023), theoretically (Frontiers Physiol, 2021) and experimentally using the model shown below (Am J Physiol, 2017). Key cardiovascular factors influencing pulse pressure amplification include the rate of change in aortic flow during late systole (closely linked to ventricular ejection dynamics), as well as the vessel radius and length from the aortic root to the periphery (Frontiers Physiol, 2021);

8. Peripheral systolic BP (pSBP, used to assess clinical risk associated with hypertension and guide acute clinical care) is mainly determined by the first shoulder of the central BP waveform (P1) and the rate of rise of the central waveform (dP/dt), differing from central systolic BP (P2) determinants. This may be a potential mechanism why BP-lowering drugs like β-blockers may have differential effects on central and peripheral BP (Am J Physiol, 2021).
   

These findings were achieved using haemodynamic algorithms we developed to:

1. Decompose the aortic BP wave into components with distinct biophysical and temporal origins, quantifying the relative contributions of cardiac and vascular properties (IEEE Trans Biomed Eng, 2021; Ann Biomed Eng, 2016);

2. Quantify the pressure wave generation and reflection at the aortic root using a novel time-varying emission coefficient (IEEE Trans Biomed Eng, 2021);


3. Reduce the number of 1-D model arterial segments by lumping them into 0-D models, demonstrating that the cPP of a distributed multisegment arterial tree can be accurately represented by a Windkessel model, preserving fidelity and full theoretical understanding of the physical meaning of the model parameters (J R Soc Interface, 2018; Am J Physiol, 2015);

4. Generate populations of thousands of virtual subjects for in silico evaluation of pulse wave indices and algorithms;


5. Obtain analytical solutions for BP and flow waveforms to enhance theoretical understanding (Frontiers Physiol, 2021; Ann Biomed Eng, 2016).