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 & References
1. WHO A global brief on hypertension. Silent killer, global public health crisis. WHO/DCO/WHD/2013 22015. 2. Mendis S, Global Atlas on Cardiovascular Disease Prevention and Control. 2011. 3. Mozaffarian et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association Circulation 2015;131(4):e 29-322. 4. Vlachopouloset al Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis Eur Heart J 2010;31(15):1865-1871.5. Mancia et al. 2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension Blood Press 2014;23(1):3-16. 6. Townsend et al. Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement from the American Heart Association Hypertension 2015;66(3):698-722. 7. Vlachopoulos et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society Atherosclerosis 2015;241(2):507-532. 8. Sharman et al. Central blood pressure measurement may improve risk stratification J Hum Hypertens 2008;22(12):838-844. 9. McEniery et al. Central pressure: variability and impact of cardiovascular risk factors: the Anglo-Cardiff Collaborative Trial II Hypertension 2008;51(6):1476-1482. 10. Herbert et al. Establishing reference values for central blood pressure and its amplification in a general healthy population and according to cardiovascular risk factors Eur Heart J 2014;35(44):3122-3133. 11. Nichols, O’Rourke, M. F. McDonald’s Blood Flow in Arteries. 5th Edition 2005:49-65. 12. O’Rourke et al. Clinical applications of arterial stiffness; definitions and reference values Am J Hypertens 2002;15(5):426-444. 13. Laurent et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications Eur Heart J 2006;27(21):2588-2605. 14. Schram et al. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study Hypertension 2004;43(2):176-181. 15. London et al. Arterial wave reflections and survival in end-stage renal failure Hypertension 2001;38(3):434-438. 16. Ben-Shlomo et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects J Am Coll Cardiol 2014;63(7):636-646. 17. Kaess et al. Aortic stiffness, blood pressure progression, and incident hypertension JAMA 2012;308(9):875-881. 18. Protogerou et al. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (Patho)-physiology, rationale and perspective on pulse pressure amplification Curr Pharm Des 2009;15(3):267-271. 19. Manisty, Hughes, A. D. Meta-analysis of the comparative effects of different classes of antihypertensive agents on brachial and central systolic blood pressure, and augmentation index Br J Clin Pharmacol 2013;75(1):79-92. 20. Trudeau. Central blood pressure as an index of antihypertensive control: determinants and potential value Can J Cardiol 2014;30(5 Suppl):S23-S28. 21. Sharman et al. Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study Hypertension 2013;62(6):1138-1145. 22. Roman et al. High central pulse pressure is independently associated with adverse cardiovascular outcome the strong heart study J Am Coll Cardiol 2009;54(18):1730-1734. 23. Weber et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease Circulation 2004;109(2):184-189. 24. Piniet al Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population: the ICARe Dicomano Study J Am Coll Cardiol 2008;51(25):2432-2439. 25. Roman et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study Hypertension 2007;50(1):197-203. 26. Williams et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study Circulation 2006;113(9):1213-1225. 27. Weber et al. Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions Eur Heart J 2005;26(24):2657-2663. 28. Hashimoto, Imai, Y., O’Rourke, M. F. Indices of pulse wave analysis are better predictors of left ventricular mass reduction than cuff pressure Am J Hypertens 2007;20(4):378-384. 29. Cruickshank et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002;106(16):2085-2090. 30. Mancia et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur Heart J 2013;34(28):2159-2219. 31. Mancia et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur Heart J 2007;28(12):1462-1536. 32. Janic, Lunder, M., Sabovic, M. Arterial stiffness and cardiovascular therapy Biomed Res Int 2014;2014:621437- 33. Koumaraset al Role of antihypertensive drugs in arterial ‘de-stiffening’ and central pulsatile hemodynamics Am J Cardiovasc Drugs 2012;12(3):143-156. 34. Lieber et al. Cardiovascular prevention: relationships between arterial aging and chronic drug treatment J Hum Hypertens 2011;25(9):524-531. 35. London et al. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol J Am Coll Cardiol 2004;43(1):92-99. 36. Mahmud, Feely, J. Beta-blockers reduce aortic stiffness in hypertension but nebivolol, not atenolol, reduces wave reflection Am J Hypertens 2008;21(6):663-667. 37. Schneider et al. Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial J Renin Angiotensin Aldosterone Syst 2008;9(1):49-56. 38. Dhakamet al Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity Am J Hypertens 2006;19(2):214-219. 39. Matsui et al. Differential Effects Between a Calcium Channel Blocker and a Diuretic When Used in Combination With Angiotensin II Receptor Blocker on Central Aortic Pressure in Hypertensive Patients Hypertension 2009;54(4):716-723. 40. Jiang et al. Superior effect of an angiotensin-converting enzyme inhibitor over a diuretic for reducing aortic systolic pressure J Hypertens 2007;25(5):1095-1099. 41. Morgan et al. Effect of different antihypertensive drug classes on central aortic pressure Am J Hypertens 2004;17(2):118-123. 42. Kampus et al. Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness Hypertension 2011;57(6):1122-1128. 43. Boutouyrie et al. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study Hypertension 2010;55(6):1314-1322. 44. Dhakamet al. A comparison of atenolol and nebivolol in isolated systolic hypertension J Hypertens 2008;26(2):351-356. 45. Mahmud, Feely, J. Antihypertensive drugs and arterial stiffness Expert Rev Cardiovasc Ther 2003;1(1):65-78. 46. Mahmud. Reducing arterial stiffness and wave reflection – Quest for the Holy Grail? Artery Research 2007;1(1):13-19. 47. Ali et al. Irbesartan improves arterial compliance more than lisinopril Vasc Health Risk Manag 2009;5(4):587-592. 48. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’ Eur Heart J 2010;31(19):2338-2350. 49. Kosmala W et al. Am J Hypertens. First published online July 7, 2015. 50. Matsui Y et al. Combined Effect of Angiotensin II Receptor Blocker and Either a Calcium Channel Blocker or Diuretic on Day-by-Day Variability of Home Blood Pressure, The Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study. Hypertension. 2012;59:1132- 1138. 51. Dahlöf B et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005 Sep 10-16;366(9489):895-906. 52. de Luca, N et al. Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects. J Hypertens. 2004 Aug;22(8):1623-30. 53. Booysen, HL et al. J Hypertens. 2013;31;1124-1130. 54. Sacco RL et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 44(7): 2064-89. 55. O’Rourke MF and Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46(1):200-4. 56. Mattace-Raso FU et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113(5):657-63. 57. Pereira T et al. Aortic stiffness is an independent predictor of stroke in hypertensive patients. Arq Bras Cardiol. 2013;100(5): 437-43. 58. Laurent S et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003;34(5): 1203-6. 59. Gasecki D et al. Pulse wave velocity is associated with early clinical outcome after ischemic stroke. Atherosclerosis. 2012;225(2):348-52 60. Gasecki D et al. Aortic stiffness predicts functional outcome in patients after ischemic stroke. Stroke. 2012;43(2):543-4. 61. Kowalczyk et al. Changes of augmentation index early after ischaemic stroke prediction functional outcome. Blood Pressure. 2020; online ahead of print.