Letter by Cameron et al Regarding Article, “Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study”
To the Editor:
We read with interest the report of the Conduit Artery Function Evaluation (CAFE) study1 showing a difference in SphygmoCor-derived central systolic blood pressure (SBP) between the 2 arms of an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy (despite similar brachial blood pressure changes).
We would make 3 points. First, the authors seem to have misinterpreted our work (authors’ Reference 53)2 as showing a “precision” of 1 mm Hg between calculated central aortic and directly measured SBP in the context of noninvasive studies. This figure relates to calibration of radial waveforms to invasive blood pressure. The correct figure for noninvasive calibration from our paper (Table 3)2 is a mean error of 7(±12) mm Hg; further, we observed a marked variability of error at similar brachial pressures. Group masking of individual variability is critical, and individual rather than group variability may preclude the reconstruction of clinically useful aortic pressures with any transfer function.3 Importantly, it is unknown whether systematic error is associated with different drug treatments. These limitations do not detract from the CAFE finding of a group difference between radial waveforms expressed as derived central pressures, but it may preclude dogmatism about any relation between derived and true aortic pressures.
Second, we note that there is no reference to heart rate–corrected augmentation index in the hazard models and point out that it is important to adjust for this confounder.1 We also note that brachial pulse pressure was as good as derived central pulse pressure in these models.
Third, ASCOT demonstrated that amlodipine/perindopril therapy was associated with better outcome.4 The CAFE substudy demonstrated that this was associated with group differences in radial waveforms and thus reconstructed central SBP by means of the SphygmoCor-generalized transfer function.1 It does not, in our opinion, address the important question of whether directing treatment according to derived estimates of central SBP will be an advantage or a disadvantage to patients with brachial hypertension. We believe that answering this question would require a different study design with treatment determined by reconstructed aortic SBP. The CAFE investigators could assist by reanalyzing their outcome data according to derived central aortic SBP. If outcome is associated with derived central SBP independent of treatment, this would provide support for an appropriately designed study.
We hope that the CAFE investigators report further follow-up and analysis, including individual rather than group variability, to help with these questions. Until such data are available, we agree with the editorialists5 that radial tonometry, with or without reconstruction of central pressures, is not ready for use in routine clinical practice. We look forward to further results that might clarify its potential clinical contribution.5
Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. 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: 1213–1225.
Smulyan H, Siddiqui DS, Carlson RJ, London GM, Safar ME. Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses. Hypertension. 2003; 42: 150–155.
Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J. 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; 366: 895–906.
Oparil S, Izzo JL Jr. Pulsology rediscovered: commentary on the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006; 113: 1162–1163.