SphygmoCor® central arterial pressure waveform analysis (PWA) provides clinicians with valuable prognostic and diagnostic information for clinical decision support. Antihypertensive therapy is a key component in the management of hypertensive patients—and there is a large body of evidence documenting the effects of pharmacological treatment on arterial stiffness, the central arterial pressure and wave reflection. [18-20] Central aortic pressure waveform guidance has been shown to positively inform hypertension management, resulting in reduced medication requirements to achieve blood pressure control with no adverse effects on left ventricular mass, cardiac function, aortic stiffness, or quality of life. 
Central arterial pressure waveform analysis using the SphygmoCor® system may provide improved, individualized therapy selection for borderline hypertensive patients or those near blood pressure goal (e.g. individuals with a brachial systolic blood pressure of 130-140mmHg), as well as improving therapy guidance in resistant hypertensive patients.
Although a reduction in brachial blood pressure remains the principle target for therapeutic treatment of hypertension, there is now evidence that some antihypertensive medications may reduce cardiovascular events due to effects that cannot be explained by brachial blood pressure alone. These effects could be explained by the protective properties of the drugs in reducing central pulsatility with resultant reduction in subclinical organ damage. Central arterial pressure waveform analysis is being used to guide the selection of antihypertensive therapy, resulting in improvements in quality of care.
There is a large body of evidence showing the differential effects of antihypertensive drugs on arterial stiffness, the central aortic pressure indices and wave reflections. [32-41,18-20] Differences can also be observed within drug classes. 19,36,42 Furthermore, central aortic blood pressure has been shown to differentiate the effects of different therapeutic combinations, as was observed in the EXPLOR [1,43] and J-CORE studies. [2,50]
The J-CORE study showed that, along with a significant reduction in central systolic blood pressure from an ARB/CCB combination, aortic pulse wave velocity in the combination therapy group was significantly lower than when combined with a diuretic, even after adjustment for mean pressure.
The ASCOT  trial included nearly 20,000 subjects having hypertension and at least three additional cardiovascular (CV) risk factors who were randomized to receive either a conventional beta blocker-based regimen (atenolol) or a calcium channel blocker-based regimen (amlodipine). By protocol, brachial blood pressure in both groups was controlled to the same level, and there were no statistical differences in brachial BP observed between the two groups. However, the amlodipine group experienced significantly fewer cardiovascular events than the atenolol group, and the study was stopped prematurely after 5-1/2 years median follow-up. A sub-set of approximately 2,000 patients from the ASCOT trial was also enrolled into the Conduit Artery Functional Evaluation (CAFE)  sub-study, the largest prospective evaluation of cardiovascular drugs on central blood pressure and hemodynamics to date. CAFE looked at the differential impact of these two drug regimens using central arterial pressure waveform analysis with SphygmoCor®. Despite no differences in brachial pressure in the two groups, a significant difference in central aortic blood pressure was observed with the Amlodipine group compared with the Atenelol group. These findings illustrate how brachial blood pressure is not always an appropriate surrogate for the effect of blood pressure-lowering drugs on arterial hemodynamics. The reduction in central aortic blood pressure may help explain the differences in clinical outcomes observed in the ASCOT trial.
The REASON  study assessed 470 high risk patients with essential hypertension for 12 months and found that perindopril-based therapy significantly reduced central systolic blood pressure and reduced left ventricular mass compared to treatment with atenolol, despite a similar reduction in brachial blood pressure between the 2 groups.35 Similar results in terms of differential effects on central blood pressure, as measured by central arterial waveform analysis, despite similar changes in brachial blood pressure have also been observed when studying the effect of different beta blockers (nebivolol vs metoprolol) in relation to reduced end-organ damage.
Importantly, the differences observed in central aortic blood pressure in these studies would not have been detected if only brachial pressure was measured. A review and meta-analysis of numerous studies on antihypertensive therapy highlighted the potential of overestimation of the effect on central systolic pressure if brachial blood pressure alone is used as a guide for treatment.
A recent study by Booysen et al. aimed to determine whether central aortic blood pressure may further refine blood pressure-related cardiovascular risk assessments (as determined by target organ changes) in individuals with normal or high normal brachial blood pressures (120-139/80-89 mmHg). The study involved 1,169 participants from a community sample of African ancestry. Central aortic blood pressure was determined with SphygmoCor®, and target organ changes were assessed from carotid-femoral pulse wave velocity (surrogate measure of aortic stiffness measured with SphygmoCor®), estimated glomerular filtration rate (eGFR), and left ventricular mass indexed to height (LVMI). Results demonstrated that normal vs. high-normal BP categories did not clearly distinguish between individuals with and without target organ damage. In contrast, normotensive individuals with aortic systolic blood pressure values that exceeded optimal thresholds demonstrated increases in pulse wave velocity (aortic stiffness) and LVMI, as well as decreases in eGFR.
Similarly, in a study by Kampus et al, central arterial pressure waveform analysis was found to better correlate with target organ damage compared to brachial pressure.  In this study, 80 hypertensive patients were randomized to receive the vasodilating beta blocker nebivolol or the cardio-selective beta blocker metoprolol. Both medications reduced heart rate and brachial pressure to the same degree, but a significant reduction in central arterial pressure waveform analysis was only observed in the nebivolol cohort. This correlated with a significant reduction in LV wall thickness, which was not observed in the metoprolol cohort. These results imply that non-invasive assessment of the central arterial pressure waveform changes may be a good surrogate for estimating reduction in left ventricular wall thickness.
The value of using central arterial pressure waveform analysis to guide hypertension management was demonstrated in the BP-GUIDE study, a prospective study of 286 hypertensive patients. The patients were randomized to treatment decisions guided by (a) best-practice usual care or by (b) best-practice usual care plus central arterial pressure waveform analysis. Patients were followed for 12 months. The use of central arterial pressure waveform analysis resulted in a significant reduction in the daily dose of medication and a cessation of medication in significantly more patients compared with those treated by best-practice usual care, while still maintaining blood pressure control and improvements in quality of life. No adverse effects were observed on LV mass, cardiac function, aortic stiffness, or quality of life. [21, 49]
Proceedings from a workshop on the clinical use of central arterial pressure waveform analysis highlighted how analysis of the waveform morphology may aid clinical decision-making in initiating and managing antihypertensive therapy in young asymptomatic individuals with systolic hypertension, guiding the choice of antihypertensive medications when additional medications are required and assessing the effects of these treatment decisions.
Hypertension and Stroke
The American Stroke Association defines stroke as any objective evidence of permanent brain, spinal, or retinal cell death due to a vascular cause.  A highly metabolic organ, the brain demands a considerable degree of blood flow, which is in part achieved through low vascular resistance. While the latter is necessary, it also leaves the brain exposed to potentially damaging excess pulsatile phenomena that occur with increased arterial stiffness . Research has shown increased aortic stiffness to be independently predictive of stroke in both healthy and hypertensive populations. [56, 57] Separate work has also shown aortic stiffness to predict fatal stroke in patients with hypertension. And while predictive value is important for the improvement in prevention strategies, central hemodynamic measurements have also demonstrated an ability to predict post stroke outcomes. Pulse Wave Velocity measured one week after stroke is an early marker of neurological improvement and also predictive of functional outcome. It has also been shown that changes in augmentation index (AIx) between days 1 and 6 post-stroke provide insights about favorable early and late functional outcome in these patients.
Central arterial pressure waveform-guided hypertension management can aid in reducing central systolic blood pressure, central arterial pressure, augmentation pressure and augmentation index, thereby preventing or reducing target organ damage and cardiovascular events. It also provides valuable information that would not be readily available from standard brachial cuff measurements regarding efficacy of antihypertensive medications.
Citations and References
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