The most exciting evidence for the utility of the reservoir-wave hypothesis comes from a recent study analysing radial arterial pressure measurements taken as part of the CAFE study (see Williams et al.). The CAFE (Conduit Artery Functional Evaluation) is a sub-study of ASCOT, a prospective trial of antihypertensive therapy (see Sever et al). In the ASCOT trial (see Williams et al.), hypertensive participants were allotted randomly to either an amlodipine or an atenolol-based therapy group and blood pressure was lowered to strictly defined limits. The participants were followed up and cardiac events (heart attacks or stroke) were recorded. It was found that the atenolol group had significantly fewer cardiac events than the amlodipine group despite having the same blood pressures. The CAFE sub-study was designed to discover differences between the groups that could explain the differences in outcomes.
We hypothesised that the difference between the groups could be related to differences in the reservoir/excess pressure based upon measurements of radial blood pressure using applanation tonometry. The reservoir pressure algorithm was applied to the pressure waveforms from 2032 subjects enrolled in the CAFE study.
A total of 134 cardiovascular events were reported after the initial measurements. Cardiovascular events were closely related to both the integral of the excess pressure over the cardiac period (HR 2.50 [1.51-4.14], p<0.001), peak excess pressure (HR 1.02 [1.00-1.04], p=0.012), and central pulse pressure calculated by the SphygmaCor device (HR 1.02 [1.00-1.03], p=0.008) in univariate models. Only the integral of excess pressure remained significant after adjustment for age and sex (HR 2.77 [1.64-4.65], p<0.001) and adjustment for Framingham Risk Score (HR 1.80 [1.02-3.16], p=0.04). HR refers to the Hazard Ratio mean [range] and p is the probability of the null hypothesis being true.
These results indicate that the integral of the excess pressure is the best of all of the indicators of cardiac incidents that were tested. These results seem to justify the utility of the reservoir-wave hypothesis which is very satisfying.
It is even more satisfying that there may be a physiological reason for this epidemiological result. If the reservoir pressure corresponds to the minimum hydraulic work that the ventricle can do to provide a given flow rate with given arterial compliance and resistance, then the integral of the excess pressure corresponds to excess work actually done by the ventricle. It seems reasonable that the greater the excess work, the more prone the ventricle will be to failure.
![[image]](pics/epi_hazard.jpg)
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This figure shows the hazard estimate based on the integral of the excess pressure (EPI) with the time of follow-up for the high (red) and low (blue) values of EPI across all subjects in the CAFE study. High and low was split at the median level. The difference after 4+ years is highly significant (p < 0.001). This suggests that the EPI may be an independent indicator of cardiac risk. |
The clinical implications of these findings are very interesting. Since the reservoir pressure, and hence the excess pressure, is dependant upon the waveform of the volume flow rate generated by the ventricle, the net compliance and the net resistance of the arterial system, it is possible to affect this in different ways by different therapies. There is very little information about how different therapies influence EPI, but the indications of the CAFE study are that this could be a very fruitful subject of research.